bluuebunny/crossref_metadata_2025 huggingface dataset:
Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
Authors: Green Richard E. , Braun Edward L. , Armstrong Joel , Earl Dent , Nguyen Ngan , Hickey Glenn , Vandewege Michael W. , St. John John A. , Capella-Gutiérrez Salvador , Castoe Todd A. , Kern Colin , Fujita Matthew K. , Opazo Juan C. , Jurka Jerzy , Kojima Kenji K. , Caballero Juan , Hubley Robert M. , Smit Arian F. , Platt Roy N. , Lavoie Christine A. , Ramakodi Meganathan P. , Finger John W. , Suh Alexander , Isberg Sally R. , Miles Lee , Chong Amanda Y. , Jaratlerdsiri Weerachai , Gongora Jaime , Moran Christopher , Iriarte Andrés , McCormack John , Burgess Shane C. , Edwards Scott V. , Lyons Eric , Williams Christina , Breen Matthew , Howard Jason T. , Gresham Cathy R. , Peterson Daniel G. , Schmitz Jürgen , Pollock David D. , Haussler David , Triplett Eric W. , Zhang Guojie , Irie Naoki , Jarvis Erich D. , Brochu Christopher A. , Schmidt Carl J. , McCarthy Fiona M. , Faircloth Brant C. , Hoffmann Federico G. , Glenn Travis C. , Gabaldón Toni , Paten Benedict , Ray David A.
Published: December 2014

To provide context for the diversification of archosaurs—the group that includes crocodilians, dinosaurs, and birds—we generated draft genomes of three crocodilians:Alligator mississippiensis(the American alligator),Crocodylus porosus(the saltwater crocodile), andGavialis gangeticus(the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
Core and region-enriched networks of behaviorally regulated genes and the singing genome
Authors: Whitney Osceola , Pfenning Andreas R. , Howard Jason T. , Blatti Charles A , Liu Fang , Ward James M. , Wang Rui , Audet Jean-Nicolas , Kellis Manolis , Mukherjee Sayan , Sinha Saurabh , Hartemink Alexander J. , West Anne E. , Jarvis Erich D.
Published: December 2014

Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ~10% of the genes in the avian genome were regulated by singing, and we found a striking regional diversity of both basal and singing-induced programs in the four key song nuclei of the zebra finch, a vocal learning songbird. The region-enriched patterns were a result of distinct combinations of region-enriched transcription factors (TFs), their binding motifs, and presinging acetylation of histone 3 at lysine 27 (H3K27ac) enhancer activity in the regulatory regions of the associated genes. RNA interference manipulations validated the role of the calcium-response transcription factor (CaRF) in regulating genes preferentially expressed in specific song nuclei in response to singing. Thus, differential combinatorial binding of a small group of activity-regulated TFs and predefined epigenetic enhancer activity influences the anatomical diversity of behaviorally regulated gene networks.
Large-scale nanoshaping of ultrasmooth 3D crystalline metallic structures
Authors: Gao Huang , Hu Yaowu , Xuan Yi , Li Ji , Yang Yingling , Martinez Ramses V. , Li Chunyu , Luo Jian , Qi Minghao , Cheng Gary J.
Published: December 2014

We report a low-cost, high-throughput benchtop method that enables thin layers of metal to be shaped with nanoscale precision by generating ultrahigh-strain-rate deformations. Laser shock imprinting can create three-dimensional crystalline metallic structures as small as 10 nanometers with ultrasmooth surfaces at ambient conditions. This technique enables the successful fabrications of large-area, uniform nanopatterns with aspect ratios as high as 5 for plasmonic and sensing applications, as well as mechanically strengthened nanostructures and metal-graphene hybrid nanodevices.
Electrons take the fast track through silicon
Authors: Spielmann Christian
Published: December 2014

Quantum-mechanical tunneling of valence-band electrons excited by intense, ultrafast laser pulses is verified with time-resolved x-ray spectroscopy

[Also see Report by

Schultze
et al.

]
Comparison of Hybribio GenoArray and Roche Human Papillomavirus (HPV) Linear Array for HPV Genotyping in Anal Swab Samples
Authors: Low Huey Chi , Silver Michelle I. , Brown Brandon J. , Leng Chan Yoon , Blas Magaly M. , Gravitt Patti E. , Woo Yin Ling
Published: December 2014

Human papillomavirus (HPV) is causally associated with anal cancer, as HPV DNA is detected in up to 90% of anal intraepithelial neoplasias and anal cancers. With the gradual increase of anal cancer rates, there is a growing need to establish reliable and clinically relevant methods to detect anal cancer precursors. In resource-limited settings, HPV DNA detection is a potentially relevant tool for anal cancer screening. Here, we evaluated the performance of the Hybribio GenoArray (GA) for genotyping HPV in anal samples, against the reference standard Roche Linear Array (LA). Anal swab samples were obtained from sexually active men who have sex with men. Following DNA extraction, each sample was genotyped using GA and LA. The overall interassay agreement, type-specific, and single and multiple genotype agreements were evaluated by kappa statistics and McNemar's χ
2
tests. Using GA and LA, 68% and 76% of samples were HPV DNA positive, respectively. There was substantial interassay agreements for the detection of all HPV genotypes (κ = 0.70, 86% agreement). Although LA was able to detect more genotypes per sample, the interassay agreement was acceptable (κ = 0.53, 63% agreement). GA had poorer specific detection of HPV genotypes 35, 42, and 51 (κ < 0.60). In conclusion, GA and LA showed good interassay agreement for the detection of most HPV genotypes in anal samples. However, the detection of HPV DNA in up to 76% of anal samples warrants further evaluation of its clinical significance.
Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013
Authors: Both Leonard , Collins Sarah , de Zoysa Aruni , White Joanne , Mandal Sema , Efstratiou Androulla
Published: December 2014

Human infections caused by toxigenic corynebacteria occur sporadically across Europe. In this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in England between January 2007 and December 2013. Epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. Molecular characterization was performed using multilocus sequence typing (MLST) alongside traditional phenotypic methods. In total, there were 20 cases of toxigenic corynebacteria; 12 (60.0%) were caused by
Corynebacterium ulcerans
, where animal contact was the predominant risk factor. The remaining eight (40.0%) were caused by
Corynebacterium diphtheriae
strains; six were biovar mitis, which were associated with recent travel abroad. Adults 45 years and older were particularly affected (55.0%; 11/20), and typical symptoms included sore throat and fever. Respiratory diphtheria with the absence of a pharyngeal membrane was the most common presentation (50.0%; 10/20). None of the eight
C. diphtheriae
cases were fully immunized. Diphtheria antitoxin was issued in two (9.5%) cases; both survived. Two (9.5%) cases died, one due to a
C. diphtheriae
infection and one due to
C. ulcerans
. MLST demonstrated that the majority (87.5%; 7/8) of
C. diphtheriae
strains represented new sequence types (STs). By adapting several primer sequences, the MLST genes in
C. ulcerans
were also amplified, thereby providing the basis for extension of the MLST scheme, which is currently restricted to
C. diphtheriae
. Despite high population immunity, occasional toxigenic corynebacterium strains are identified in England and continued surveillance is required.
Hepatitis B Virus Polymerase Disrupts K63-Linked Ubiquitination of STING To Block Innate Cytosolic DNA-Sensing Pathways
Authors: Liu Yinghui , Li Jianhua , Chen Jieliang , Li Yaming , Wang Weixia , Du Xiaoting , Song Wuhui , Zhang Wen , Lin Li , Yuan Zhenghong
Published: December 2014

The cellular innate immune system recognizing pathogen infection is essential for host defense against viruses. In parallel, viruses have developed a variety of strategies to evade the innate immunity. The hepatitis B virus (HBV), a DNA virus that causes chronic hepatitis, has been shown to inhibit RNA helicase RIG-I-mediated interferon (IFN) induction. However, it is still unknown whether HBV could affect the host DNA-sensing pathways. Here we report that in transiently HBV-transfected Huh7 cells, the stably HBV-producing cell line HepAD38, and HBV-infected HepaRG cells and primary human hepatocytes, HBV markedly interfered with IFN-β induction and antiviral immunity mediated by the stimulator of interferon genes (STING), which has been identified as a central factor in foreign DNA recognition and antiviral innate immunity. Screening analysis demonstrated that the viral polymerase (Pol), but not other HBV-encoded proteins, was able to inhibit STING-stimulated interferon regulatory factor 3 (IRF3) activation and IFN-β induction. Moreover, the reverse transcriptase (RT) and the RNase H (RH) domains of Pol were identified to be responsible for the inhibitory effects. Furthermore, Pol was shown to physically associate with STING and dramatically decrease the K63-linked polyubiquitination of STING via its RT domain without altering the expression level of STING. Taken together, these observations suggest that besides its inherent catalytic function, Pol has a role in suppression of IFN-β production by direct interaction with STING and subsequent disruption of its K63-linked ubiquitination, providing a new mechanism for HBV to counteract the innate DNA-sensing pathways.

IMPORTANCE
Although whether and how HBV infection induces the innate immune responses are still controversial, it has become increasingly clear that HBV has developed strategies to counteract the pattern recognition receptor-mediated signaling pathways. Previous studies have shown that type I IFN induction activated by the host RNA sensors could be inhibited by HBV. However, it remains unknown whether HBV as a DNA virus utilizes evasion mechanisms against foreign DNA-elicited antiviral signaling. In recent years, the cytosolic DNA sensor and key adaptor STING has been demonstrated to be essential in multiple foreign DNA-elicited innate immune signalings. Here, for the first time, we report STING as a new target of HBV to antagonize IFN induction and identify the viral polymerase responsible for the inhibitory effect, thus providing an additional molecular mechanism by which HBV evades the innate immunity; this implies that in addition to its inherent catalytic function, HBV polymerase is a multifunctional immunomodulatory protein.
Expanding the Role of the Virome: Commensalism in the Gut
Authors: Cadwell Ken
Published: December 2014

Viruses affect host physiology beyond causing acute disease, thereby giving rise to the concept that the virome is a component of the microbiome. However, the role of the enteric virome is understudied relative to the fast-paced research examining commensal bacteria in the intestine. In this article, I discuss our recent work on murine norovirus indicating that an animal virus in the intestine can provide many of the signals to the host that have been attributed to commensal bacteria. Our findings suggest that the surge in microbiome research should incorporate examination of the enteric virome.
Characterization of Novel Transcripts of Human Papillomavirus Type 16 Using Cap Analysis Gene Expression Technology
Authors: Taguchi Ayumi , Nagasaka Kazunori , Kawana Kei , Hashimoto Kosuke , Kusumoto-Matsuo Rika , Plessy Charles , Thomas Miranda , Nakamura Hiroe , Bonetti Alessandro , Oda Katsutoshi , Kukimoto Iwao , Carninci Piero , Banks Lawrence , Osuga Yutaka , Fujii Tomoyuki
Published: December 2014

We have performed cap-analysis gene expression (CAGE) sequencing to identify the regulatory networks that orchestrate genome-wide transcription in human papillomavirus type 16 (HPV16)-positive cervical cell lines of different grades: W12E, SiHa, and CaSki. Additionally, a cervical intraepithelial neoplasia grade 1 (CIN1) lesion was assessed for identifying the transcriptome expression profile. Here we have precisely identified a novel antisense noncoding viral transcript in HPV16. In conclusion, CAGE sequencing should pave the way for understanding a diversity of viral transcript expression.
Mutations within the Pathogenic Region of Herpes Simplex Virus 1 gK Signal Sequences Alter Cell Surface Expression and Neurovirulence
Authors: Matundan Harry H. , Mott Kevin R. , Akhtar Aslam Abbasi , Breunig Joshua J. , Ghiasi Homayon
Published: December 2014

To investigate the role of the signal sequences of herpes simplex virus 1 (HSV-1) gK on virus replication and viral pathogenesis, we constructed recombinant viruses with or without mutations within the signal sequences of gK. These recombinant viruses expressed two additional copies of the mutated (MgK) or native (NgK) form of the gK gene in place of the latency-associated transcript with a myc epitope tag to facilitate detection at their 3′ ends. The replication of MgK virus was similar to that of NgK both
in vitro
and
in vivo
, as well as in the trigeminal ganglia (TG) of latently infected mice. The levels of gB and gK transcripts in the corneas, TG, and brains of infected mice on days 3 and 5 postinfection were markedly virus and time dependent, as well as tissue specific. Mutation in the signal sequence of gK in MgK virus blocked cell surface expression of gK-myc in rabbit skin cells, increased 50% lethal dose, and decreased corneal scarring in ocularly infected mice compared to the NgK or revertant (RgK) virus. MgK and NgK viruses, and not the RgK virus, showed a reduced extent of explant reactivation at the lower dose of ocular infection but not at the higher dose. However, the time of reactivation was not affected by overexpression of the different forms of gK. Taken together, these results strongly suggest that the 8mer peptide (ITAYGLVL) within the signal sequence of gK promotes cell surface expression of gK in infected cells and ocular pathogenesis in infected mice.

IMPORTANCE
In this study, we show for the first time that mutations within the signal sequence of gK blocked cell surface expression of inserted recombinant gK
in vitro
. Furthermore, this blockage in cell surface expression was correlated with higher 50% lethal dose and less corneal scarring
in vivo
. Thus, these studies point to a key role for the 8mer within the signal sequence of gK in HSV-1-induced pathogenicity.
Clinician-friendly lower extremity physical performance measures in athletes: a systematic review of measurement properties and correlation with injury, part 1. The tests for knee function including the hop tests
Authors: Hegedus Eric J , McDonough Suzanne , Bleakley Chris , Cook Chad E , Baxter G David
Published: December 2014

Objective

To review the measurement properties of physical performance tests (PPTs) of the knee as each pertain to athletes, and to determine the relationship between PPTs and injury in athletes age 12 years to adult.

Methods

A search strategy was constructed by combining the terms ‘lower extremity’ and synonyms for ‘performance test’, and names of performance tests with variants of the term ‘athlete’. In this, part 1, we report on findings in the knee. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed and theConsensus-basedStandards for the selection of healthMeasurementInstruments (COSMIN) checklist was used to critique the methodological quality of each paper. A second measure was used to analyse the quality of the measurement properties of each test.

Results

In the final analysis, we found 29 articles pertinent to the knee detailing 19 PPTs, of which six were compiled in a best evidence synthesis. The six tests were: one leg hop for distance (single and triple hop), 6 m timed hop, crossover hop for distance, triple jump and single leg vertical jump. The one leg hop for distance is the most often studied PPT. There is conflicting evidence regarding the validity of the hop and moderate evidence that the hop test is responsive to changes during rehabilitation. No test has established reliability or measurement error as assessed by the minimal important change or smallest detectable change. No test predicts knee injury in athletes.

Conclusions

Despite numerous published articles addressing PPTs at the knee, there is predominantly limited and conflicting evidence regarding the reliability, agreement, construct validity, criterion validity and responsiveness of commonly used PPTs. There is a great opportunity for further study of these tests and the measurement properties of each in athletes.
A district general hospital experience of palliative biliary stenting
Authors: Thomas S E , Lee M J , Sivaramakrishnan N , Lambert K
Published: December 2014

Background

Palliative management of malignant pancreaticobiliary (PB) disease typically takes the form of endoscopic biliary stenting with a covered metal stent. We set out to assess outcomes from endoscopic biliary stenting (endoscopic retrograde cholangiopancreatography, ERCP) for malignant disease in our district general hospital (DGH).

Methods

We identified patients with malignant PB disease who underwent primary ERCP between 2011 and 2012. Case notes were reviewed for clinical outcomes and involvement of palliative care.

Results

38 patients underwent biliary stenting in this period. Median age was 75.6 years (53.6–99.8 years). 35 stents were placed for primary PB malignancy. 31 of these stents were covered metal stents and 6 were uncovered. Bilirubin decreased from a median of 218 to 112 µmol/L (median decrease 55 µmol/L). Complications occurred in the following 13 cases: 7 blocked stents (18.9%), 2 of which were associated with sepsis; 2 cases of stent migration (8.1%); 3 cases of biliary sepsis (8.1%) and 1 episode of pancreatitis (2.7%). Subsequently, 12 patients underwent a single repeat ERCP and 1 patient underwent 3 further ERCPs. Median survival following ERCP and stent was 78 days (10–806). 28 patients (76%) were known to the hospital palliative care team.

Conclusions

Our DGH provides local service with complication rates comparable to those described in the literature. This allows care of patients with limited prognosis to be treated close to home. The majority of stent complications and mortality occur within 3 months. Input from the palliative care team is useful when considering whether a patient has a prognosis long enough to benefit from the procedure.
An analytic bilateral Laplace–Feynman transform on Hilbert space
Authors: Chang Seung Jun , Choi Jae Gil
Published: December 2014

In this paper, we examine the analytic bilateral Laplace–Feynman transform (BLFT) for functions on the Hilbert space H. We then proceed to establish a relationship between the analytic BLFT on H and the analytic Fourier–Feynman transform on the abstract Wiener space B.
Generalized scale-free homophilic network
Authors: Dos Santos A. M. , De Almeida M. L. , Mendes G. A. , Da Silva L. R.
Published: December 2014

We propose a simple network growth process where the preferential attachment contains two essential parameters: homophily, namely, the tendency of sites to link with similar ones, and the number of attaching neighbors. It jointly generalizes the Barabási–Albert model and the scale-free homophilic model with a control parameter which tunes the importance of the homophily on preferential attachment process. Our results support a detailed discussion about different kinds of correlation, in special a fitness correlation introduced in this paper, and comparisons between BA model, scale-free homophilic model, and our present model considering its topological properties: degree distribution, time dependence of the connectivity and clustering coefficient.
Dark spatial solitons splitting in logarithmically saturable nonlinear media
Authors: Zhang Yuhong , Liu Baoyuan , Lu Keqing , Liu Wangyun , Han Jun
Published: December 2014

We numerically simulate the evolution of the dark-notch-bearing optical beam in the logarithmically saturable nonlinear media based on beam propagation method (BPM). The simulation results indicate that the multiple dark spatial solitons are deep, possible in this type of nonlinear media. The number of multiple dark spatial solitons depends on the width of the dark notch, the initial conditions and the peak intensity of the initial input beam. Under the odd and even initial conditions, the odd and even number sequence of multiple dark spatial solitons can be obtained, respectively. For an input beam with fixed optical intensity, the number of dark solitons increases with the width of the initial input dark notch. The behavior of the multiple dark solitons in this type of media is similar to that in a photorefractive nonlinear crystal.
CONSTANT MATURITY TREASURY CONVEXITY CORRECTION
Authors: PUCCI MARIO
Published: December 2014

In a Constant Maturity Treasury (CMT) swap the exotic leg pays, for a given tenor, the yield-to-maturity computed out of a reference bond curve. This paper introduces a theoretical framework for the modelling of CMT that takes into account default risk of bond issuer. As an application, we obtain, under simple but standard assumptions, analytical convexity corrections for some fundamental payoffs contingent on the CMT.
A New Method To Solve Bi-Level Quadratic Linear Fractional Programming Problems
Authors: Singh Sanjeet , Haldar Nivedita
Published: December 2014

In this paper, we have developed a new method to solve bi-level quadratic linear fractional programming (BLQLFP) problems in which the upper-level objective function is quadratic and the lower-level objective function is linear fractional. In this method a BLQLFP problem is transformed into an equivalent single-level quadratic programming (QP) problem with linear constraints by forcing the duality gap of the lower-level problem to zero. Then by obtaining all vertices of the constraint region of the dual of the lower-level problem, which is a convex polyhedron, the single-level QP problem is converted into a series of finite number of QP problems with linear constraints which can be solved by any standard method for solving a QP. The best among the optimal solutions gives the desired optimal solution for the original bi-level programming (BLP) problem. Theoretical results have been illustrated with the help of a numerical example.
Being Credit Rationed: Delay and Transaction Cost
Authors: Mallik Rajlakshmi
Published: December 2014

This paper develops alternative models explaining why households with credit need to finance their projects (enterprises) avoid formal credit. More importantly it argues that the problem of avoidance of formal credit and ensuring credit access is not necessarily restricted to the small borrower or borrowers with inefficient projects. Delay cost and personal loan transaction cost may also cause highly productive projects or larger projects shying away from formal credit in spite of low interest rates. Some of the policy implications of the above findings are also discussed.
Electric Control of Friction on Silicon Studied by Atomic Force Microscope
Authors: Jiang Yan , Yue Lili , Yan Boshen , Liu Xi , Yang Xiaofei , Tai Guoan , Song Juan
Published: December 2014

We investigated friction on an n-type silicon surface using an atomic force microscope when a bias voltage was applied to the sample. Friction forces on the same track line were measured before and after the bias voltages were applied and it was found that the friction forces in n-type silicon can be tuned reversibly with the bias voltage. The dependence of adhesion forces between the silicon nitride tip and Si sample on the bias voltages approximately follows a parabolic law due to electrostatic force, which results in a significant increase in the friction force at an applied electric field.
Almost periodic solutions of nonautonomous Lotka–Volterra competitive systems with dominated delays
Authors: Feng Chunhua , Huang Jianmin
Published: December 2014

In this paper, a class of nonautonomous Lotka–Volterra type multispecies competitive systems with delays is studied. By employing Lyapunov functional, some sufficient conditions to guarantee the existence of almost periodic solutions for the Lotka–Volterra system are obtained.
Permanence and extinction for a nonautonomous schistosomiasis model with saturation incidence rate
Authors: Xie Dehui , Zhang Xiangyu , Yan Shuixian , Gao Shujing
Published: December 2014

In the real world, quite a few infectious diseases like schistosomiasis spread seasonally. In this paper, a nonautonomous schistosomiasis system is established, in which the saturation incidence rate and the coefficients varying with time are taken into account. The long-time behavior of the model is studied. Under quite weak assumptions, sufficient conditions for the permanence and extinction of infectious population of disease are obtained. Finally, numerical simulations illustrate the validity of our results.
Controls on deltaic sedimentation in glacio-eustatic cycles of late Marsdenian (Namurian R
2b
4 to R
2c
1, Pennsylvanian) age in the UK Central Pennine Basin
Authors: Jones C. M.
Published: December 2014

Evolution of the succession between the
Bilinguites eometabilinguis
(R
2b
4) and
Verneulites sigma
(R
2c
2) marine bands of Marsdenian (Pennsylvanian) age in the Central Pennine Basin, and its offshore extension into the North Sea Basin, is discussed. Five separate marine bands are now recognized. Two closely spaced marine bands,
B. eometabilinguis
and
B. metabilinguis
, occur at the base of the R
2b
4 cycle and a higher
B. metabilinguis
band occurs at the base of the R
2b
5 cycle. The overlying
B. superbilinguis
and
V. sigma
marine bands define an additional thinner and much simpler cycle (R
2c
1). These three cycles are all of glacio-eustatic origin. A new sequence-stratigraphic interpretation examines the relationship between the constituent sandstone units (currently named the Hazel Greave Grit, Beacon Hill Flags, Guiseley Grit, Ashover Grit, Roaches Grit, plus local names and unnamed units). Different types of fluvial-deltaic sequences were deposited in different phases of the cycle and some cycles lack coarse clastic lithologies. The succession in parts of Yorkshire and Lancashire contains a major non-sequence in the R
2b
5 cycle. A revised interpretation of the incised deep channels in the Roaches Grit in Staffordshire, suggesting river channel adjustment to a post-glacial climate rather than infill of a pre-eroded palaeovalley, is also presented. Many of these different features can be explained by climatic variations associated with the Carboniferous Ice Age. Variations in basin bathymetry and fault related subsidence exercised more localized controls.
Geology and geomorphology of the Palaeolithic site at High Lodge, Mildenhall, Suffolk, England
Authors: West R.G. , Gibbard P.L. , Boreham S. , Rolfe C.
Published: December 2014

The geology of the High Lodge site at Mildenhall is described and re-interpreted as a sequence of deposits related to a doline formed in the underlying Chalk. Doline development in the area is considered in detail. Lacustrine sediments filling the depression contain a Palaeolithic industry and pollen assemblages that indicate contemporaneous coniferous woodland. The High Lodge sequence, at the northern end of the Warren Hill ridge, is related to the Three Hills site at the southern end of the ridge and to recent exposures near the Beech Clump, midway on the ridge. The geology of the three sites combines to demonstrate a series of ice-marginal proglacial successions along the west and south side of the Warren Hill ridge, marking a glacial limit. This Skertchly Line limit, on the eastern flank of the Fenland, resulted from the Tottenhill ice advance into Fenland late in the Wolstonian Stage (
c
. 160 ka; during Marine Isotope Stage [MIS] 6). Structural evidence indicates that the doline filling was initially thrust glaciotectonically by the glacial ice. These sediments were subsequently disturbed by diapirism arising from loading by meltwater deposits and possibly by periglacial processes. The doline strata predate the ice advance and represent a period of cool temperate vegetation, probably of interstadial character, earlier in the Wolstonian, during MIS 7. The High Lodge Palaeolithic industry is associated with this cool temperate period, not with pre-Anglian times as formerly proposed. At Three Hills, artefacts occur within the proglacial deposits and are reworked from an earlier period. The geomorphology of the Warren Hill ridge is described and an interpretation of the ice front presented. The relation of the area to the wider Fenland landscape development is discussed.
Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks
Authors: Carey Shawn P. , Rahman Aniqua , Kraning-Rush Casey M. , Romero Bethsabe , Somasegar Sahana , Torre Olivia M. , Williams Rebecca M. , Reinhart-King Cynthia A.
Published: December 2014

Tumor cell invasion through the stromal extracellular matrix (ECM) is a key feature of cancer metastasis, and understanding the cellular mechanisms of invasive migration is critical to the development of effective diagnostic and therapeutic strategies. Since cancer cell migration is highly adaptable to physiochemical properties of the ECM, it is critical to define these migration mechanisms in a context-specific manner. Although extensive work has characterized cancer cell migration in two- and three-dimensional (3D) matrix environments, the migration program employed by cells to move through native and cell-derived microtracks within the stromal ECM remains unclear. We previously reported the development of an in vitro model of patterned type I collagen microtracks that enable matrix metalloproteinase-independent microtrack migration. Here we show that collagen microtracks closely resemble channel-like gaps in native mammary stroma ECM and examine the extracellular and intracellular mechanisms underlying microtrack migration. Cell-matrix mechanocoupling, while critical for migration through 3D matrix, is not necessary for microtrack migration. Instead, cytoskeletal dynamics, including actin polymerization, cortical tension, and microtubule turnover, enable persistent, polarized migration through physiological microtracks. These results indicate that tumor cells employ context-specific mechanisms to migrate and suggest that selective targeting of cytoskeletal dynamics, but not adhesion, proteolysis, or cell traction forces, may effectively inhibit cancer cell migration through preformed matrix microtracks within the tumor stroma.
Vitamin D receptor agonist VS-105 improves cardiac function in the presence of enalapril in 5/6 nephrectomized rats
Authors: Wu-Wong J. Ruth , Chen Yung-wu , Wessale Jerry L.
Published: December 2014

Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). Patients with CKD experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRA therapy may be associated with cardio-renal protective and survival benefits in patients with CKD. The 5/6 nephrectomized (NX) Sprague-Dawley rat with established uremia exhibits elevated serum parathyroid hormone (PTH), hypertension, and abnormal cardiac function. Treatment of 5/6 NX rats with VS-105, a novel VDRA (0.05 and 0.5 μg/kg po by gavage), once daily for 8 wk in the presence or absence of enalapril (30 mg/kg po via drinking water) effectively suppressed serum PTH without raising serum calcium. VS-105 alone reduced systolic blood pressure (from 174 ± 6 to 145 ± 9 mmHg, P < 0.05) as effectively as enalapril (from 174 ± 6 to 144 ± 7 mmHg, P < 0.05). VS-105 improved cardiac functional parameters such as E/A ratio, ejection fraction, and fractional shortening with or without enalapril. Enalapril or VS-105 alone significantly reduced left ventricular hypertrophy (LVH); VS-105 plus enalapril did not further reduce LVH. VS-105 significantly reduced both cardiac and renal fibrosis. The lack of hypercalcemic toxicity of VS-105 is due to its lack of effects on stimulating intestinal calcium transport and inducing the expression of intestinal calcium transporter genes such as Calb3 and TRPV6. These studies demonstrate that VS-105 is a novel VDRA that may provide cardiovascular benefits via VDR activation. Clinical studies are required to confirm the cardiovascular benefits of VS-105 in CKD.
A functional (pro)renin receptor is expressed in human lymphocytes and monocytes
Authors: Narumi Kaori , Hirose Takuo , Sato Emiko , Mori Takefumi , Kisu Kiyomi , Ishikawa Mayuko , Totsune Kazuhito , Ishii Tomonori , Ichihara Atsuhiro , Nguyen Genevieve , Sato Hiroshi , Ito Sadayoshi
Published: December 2014

The renin-angiotensin system (RAS) is involved in inflammation. The signaling via the ANG II type 1 receptor in human lymphocytes and monocytes, which play key roles in pathophysiology of glomerulonephritis (GN), can enhance inflammation. However, the role of the (pro)renin receptor [(P)RR], a component of the RAS, in inflammatory reactions is unknown. We assessed whether (P)RR is expressed in human lymphocytes and monocytes by RT-PCR, Western blotting, flow cytometry, and immunohistochemistry, and whether (P)RR functions in inflammation. (P)RR mRNA and protein were expressed in human peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis revealed high expression of (P)RR on monocytes. (P)RR was present on PBMCs, infiltrating lymphocytes, and macrophages around glomeruli with a crescent in anti-neutrophil cytoplasmic antibody (ANCA)-associated GN. Renin stimulation of PBMCs from healthy subjects in the presence of the ANG II type 1 receptor and ANG II type 2 receptor blockers induced ERK1/2 phosphorylation and release of IL-6 and expression of cyclooxygenase-2 (COX-2). The increases in cytokine release and COX-2 expression were inhibited in the presence of an ERK1/2 inhibitor. (P)RR knockdown by small interfering RNA in U937 cells, a human leukemic monocyte lymphoma cell line, significantly decreased ERK1/2 phosphorylation after renin stimulation. Thus (P)RR expressed in human inflammatory cells might contribute to inflammation in ANCA-associated GN.
IL-1 receptor blockade alleviates endotoxin-mediated impairment of renal drug excretory functions in rats
Authors: Kadova Zuzana , Dolezelova Eva , Cermanova Jolana , Hroch Milos , Laho Tomas , Muchova Lucie , Staud Frantisek , Vitek Libor , Mokry Jaroslav , Chladek Jaroslav , Havlinova Zuzana , Holecek Milan , Micuda Stanislav
Published: December 2014

The aim of our study was to investigate whether two potent anti-inflammatory agents, dexamethasone and anakinra, an IL-1 receptor antagonist, may influence acute kidney injury (AKI) and associated drug excretory functions during endotoxemia (LPS) in rats. Ten hours after LPS administration, untreated endotoxemic rats developed typical symptoms of AKI, with reduced GFR, impaired tubular excretion of urea and sodium, and decreased urinary excretion of azithromycin, an anionic substrate for multidrug resistance-transporting proteins. Administration of both immunosuppressants attenuated the inflammatory response, liver damage, AKI, and increased renal clearance of azithromycin mainly by restoration of GFR, without significant influence on its tubular secretion. The lack of such an effect was related to the differential effect of both agents on the renal expression of individual drug transporters. Only dexamethasone increased the urinary clearance of bile acids, in accordance with the reduction of the apical transporter (Asbt) for their tubular reabsorption. In summary, our data demonstrated the potency of both agents used for the prevention of AKI, imposed by endotoxins, and for the restoration of renal drug elimination, mainly by the improvement of GFR. The influence of both drugs on altered tubular functions and the expression of drug transporters was differential, emphasizing the necessity of knowledge of transporting pathways for individual drugs applied during sepsis. The effect of anakinra suggests a significant contribution of IL-1 signaling to the pathogenesis of LPS-induced AKI.
Deciphering physiological role of the mechanosensitive TRPV4 channel in the distal nephron
Authors: Mamenko M. , Zaika O. , Boukelmoune N. , O'Neil R. G. , Pochynyuk O.
Published: December 2014

Long-standing experimental evidence suggests that epithelial cells in the renal tubule are able to sense osmotic and pressure gradients caused by alterations in ultrafiltrate flow by elevating intracellular Ca2+concentration. These responses are viewed as critical regulators of a variety of processes ranging from transport of water and solutes to cellular growth and differentiation. A loss in the ability to sense mechanical stimuli has been implicated in numerous pathologies associated with systemic imbalance of electrolytes and to the development of polycystic kidney disease. The molecular mechanisms conferring mechanosensitive properties to epithelial tubular cells involve activation of transient receptor potential (TRP) channels, such as TRPV4, allowing direct Ca2+influx to increase intracellular Ca2+concentration. In this review, we critically analyze the current evidence about signaling determinants of TRPV4 activation by luminal flow in the distal nephron and discuss how dysfunction of this mechanism contributes to the progression of polycystic kidney disease. We also review the physiological relevance of TRPV4-based mechanosensitivity in controlling flow-dependent K+secretion in the distal renal tubule.
Predicting Visual Outcomes for Macula-Off Rhegmatogenous Retinal Detachment with Optical Coherence Tomography
Authors: Suzuki Noriyuki , Kunikata Hiroshi , Aizawa Naoko , Abe Toshiaki , Nakazawa Toru
Published: December 2014

Purpose.We evaluated the ability of novel optical coherence tomography (OCT) parameters to predict postoperative best-corrected visual acuity (BCVA) in macula-off rhegmatogenous retinal detachment (RRD) eyes.Methods.We reviewed the medical records of 56 consecutive eyes with macula-off RRD. Clinical findings were analyzed including the relationship between preoperative OCT findings and 6-month postoperative BCVA.Results.Six-month postoperative BCVA was significantly correlated with preoperative findings including retinal height at the fovea, total and inner layer cross-sectional macular area within 2 mm of the fovea, and preoperative BCVA (P<0.001,P<0.001,P=0.001, andP<0.001, resp.). Multiple regression analysis revealed that the duration of macular detachment and total cross-sectional macular area were independent factors predicting 6-month postoperative BCVA (P=0.024andP=0.041, resp.).Conclusions.Measuring preoperative total cross-sectional area of the macular layer within 2 mm of the fovea with OCT is a useful and objective way to predict postoperative visual outcome in eyes with macula-off RRD.
Epidemic Model of Leptospirosis Containing Fractional Order
Authors: Khan Muhammad Altaf , Saddiq S. F. , Islam Saeed , Khan Ilyas , Ching Dennis Ling Chuan
Published: December 2014

We study an epidemic model of leptospirosis in fractional order numerically. The multistep generalized differential transform method is applied to find the accurate approximate solution of the epidemic model of leptospirosis disease in fractional order. A unique positive solution for the epidemic model in fractional order is presented. For the integer case derivative, the approximate solution of MGDTM is compared with the Runge-Kutta order four scheme. The numerical results are presented for the justification purpose.
KCHO‐1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide‐Induced Neuroinflammatory Responses through Nrf2‐Mediated Heme Oxygenase‐1 Expression in Mouse BV2 Microglia Cells
Authors: Lee Dong-Sung , Ko Wonmin , Yoon Chi-Su , Kim Dong-Cheol , Yun Jinju , Lee Jun-Kyung , Jun Ki-Young , Son Ilhong , Kim Dong-Woung , Song Bong-Keun , Choi Seulah , Jang Jun-Hyeog , Oh Hyuncheol , Kim Sungchul , Kim Youn-Chul
Published: December 2014

The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)‐1 and to determine their mechanism of action in neurodegenerative diseases. KCHO‐1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO‐1 in lipopolysaccharide‐ (LPS‐) treated mouse BV2 microglia. KCHO‐1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS‐derived nitric oxide (NO), cyclooxygenase‐ (COX‐) 2, and COX‐2‐derived prostaglandin E2 (PGE2) in LPS‐stimulated BV2 microglia. It also reduced tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B‐α (IκB‐α) phosphorylation and degradation and nuclear factor kappa B (NF‐κB) translocation and DNA binding. Additionally, KCHO‐1 upregulated HO‐1 expression by promoting nuclear translocation of nuclear factor E2‐related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO‐1 on proinflammatory mediators and proteins associated with HO‐1 expression. Our data suggest that KCHO‐1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation.
Effect of DiD Carbocyanine Dye Labeling on Immunoregulatory Function and Differentiation of Mice Mesenchymal Stem Cells
Authors: Mohtasebi Maryam Sadat , Nasri Fatemeh , Kamali Sarvestani Eskandar
Published: December 2014

Mesenchymal stem cells (MSCs) have been used to treat a variety of degenerative disorders. Labeling of MSCs with an appropriate tracer is vital to demonstrate thein vivoengraftment and differentiation of transplanted MSCs. DiD is a lipophilic fluorescent dye with near infrared emission spectra that makes it suitable forin vivotracing. Therefore, in the present study the consequences of DiD labeling on induction of oxidative stress and apoptosis as well as inhibition of biological functions of mesenchymal stem cells (MSCs) were investigated. DiD labeling did not provoke the production of ROS, induction of apoptosis, or inhibition of production of immunosuppressive factors (PGE2 and IL-10) by MSCs. In addition, there were no statistical differences between DiD-labeled and unlabeled MSCs in suppression of proliferation and cytokine production (IFN-γand IL-17) byin vitrostimulated splenocytes or improvement of clinical score in EAE afterin vivoadministration. In addition, DiD labeling did not alter the differentiation capacity of MSCs. Taken together, DiD can be considered as a safe dye forin vivotracking of MSCs.
Two‐Stage Chaos Optimization Search Application in Maximum Power Point Tracking of PV Array
Authors: Wang Lihua , Wei Xueye , Zhu Tianlong , Zhang Junhong
Published: December 2014

In order to deliver the maximum available power to the load under the condition of varying solar irradiation and environment temperature, maximum power point tracking (MPPT) technologies have been used widely in PV systems. Among all the MPPT schemes, the chaos method is one of the hot topics in recent years. In this paper, a novel two‐stage chaos optimization method is presented which can make search faster and more effective. In the process of proposed chaos search, the improved logistic mapping with the better ergodic is used as the first carrier process. After finding the current optimal solution in a certain guarantee, the power function carrier as the secondary carrier process is used to reduce the search space of optimized variables and eventually find the maximum power point. Comparing with the traditional chaos search method, the proposed method can track the change quickly and accurately and also has better optimization results. The proposed method provides a new efficient way to track the maximum power point of PV array.
Multiresolution Analysis Based on Coalescence Hidden-Variable Fractal Interpolation Functions
Authors: Kapoor G. P. , Prasad Srijanani Anurag
Published: December 2014

Multiresolution analysis arising from Coalescence Hidden-variable Fractal Interpolation Functions (CHFIFs) is developed. The availability of a larger set of free variables and constrained variables with CHFIF in multiresolution analysis based on CHFIFs provides more control in reconstruction of functions in L2(R) than that provided by multiresolution analysis based only on Affine Fractal Interpolation Functions (AFIFs). Our approach consists of introduction of the vector space of CHFIFs, determination of its dimension and construction of Riesz bases of vector subspaces Vk, k∈Z, consisting of certain CHFIFs in L2(R)∩C0(R).
Long Term Solar Radiation Forecast Using Computational Intelligence Methods
Authors: Coelho João Paulo , Boaventura-Cunha José
Published: December 2014

The point prediction quality is closely related to the model that explains the dynamic of the observed process. Sometimes the model can be obtained by simple algebraic equations but, in the majority of the physical systems, the relevant reality is too hard to model with simple ordinary differential or difference equations. This is the case of systems with nonlinear or nonstationary behaviour which require more complex models. The discrete time-series problem, obtained by sampling the solar radiation, can be framed in this type of situation. By observing the collected data it is possible to distinguish multiple regimes. Additionally, due to atmospheric disturbances such as clouds, the temporal structure between samples is complex and is best described by nonlinear models. This paper reports the solar radiation prediction by using hybrid model that combines support vector regression paradigm and Markov chains. The hybrid model performance is compared with the one obtained by using other methods like autoregressive (AR) filters, Markov AR models, and artificial neural networks. The results obtained suggests an increasing prediction performance of the hybrid model regarding both the prediction error and dynamic behaviour.