bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of monolayer–multilayer PVD nitride coating
Authors: Upadhyay R. K. , Kumaraswamidhas L. A.
Published: August 2014

A thin monolayer and multilayer physical vapour deposition film was prepared on tool steel substrates using an unbalanced magnetron sputtering technique. Characteristics of multilayer (Mo/MoN, Ti/TiN, Cr/CrN, W/W2N; A/ B = 0·6∶0·3 μm) and monolayer (MoN, TiN, CrN, W2N; 0·6 μm) coatings were investigated concerning the phase composition and coating adhesion. The multilayer film sliding against alumina (Al2O3) and steel balls (100Cr6) had good wear resistance and very long service life at room temperature compared to monolayer analogues. In order to evaluate the drilling performance in wet condition four surfactants, i.e. zinc dithiodiphosphate, sodium dodecyl sulphate, sodium hexametaphosphate and cetyl trimethylammonium bromide as 1 wt-% were used with polyalphaolefin base oil. A significant reduction in flank wear rate was measured under wet condition.
Aspirin-triggered 15-epi-lipoxin A4 regulates neutrophil-platelet aggregation and attenuates acute lung injury in mice
Authors: Ortiz-Muñoz Guadalupe , Mallavia Beñat , Bins Adriaan , Headley Mark , Krummel Matthew F. , Looney Mark R.
Published: August 2014

Key Points

Neutrophil-platelet aggregates are dynamically formed in the lung in response to injury and are regulated by aspirin-triggered lipoxin. The therapeutic effect of aspirin in acute lung injury is in large part mediated by the production of pro-resolving lipid mediators.
On lacunary statistical boundedness
Authors: Bhardwaj Vinod K , Gupta Sandeep , Mohiuddine Syed A , Kılıçman Adem
Published: August 2014

A new concept of lacunary statistical boundedness is introduced. It is shown that, for a given lacunary sequenceθ={kr}, a sequence{xk}is lacunary statistical bounded if and only if for ‘almost allkw.r.t.θ’, the valuesxkcoincide with those of a bounded sequence. Apart from studying various algebraic properties and computing the Köthe-Toeplitz duals of the spaceSθ(b)of all lacunary statistical bounded sequences, a decomposition theorem is also established. We characterize thoseθfor whichSθ(b)=S(b). Finally, we give a general description of inclusion between two arbitrary lacunary methods of statistical boundedness.

MSC:40C05, 40A05, 46A45.
pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers
Authors: Alba María , Formentín Pilar , Ferré-Borrull Josep , Pallarès Josep , Marsal Lluís F
Published: August 2014

We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release.
Effects of macro- versus nanoporous silicon substrates on human aortic endothelial cell behavior
Authors: Formentín Pilar , Alba María , Catalán Úrsula , Fernández-Castillejo Sara , Pallarès Josep , Solà Rosà , Marsal Lluís F
Published: August 2014

Human aortic endothelial cells play a key role in the pathogenesis of atherosclerosis, which is a common, progressive, and multifactorial disease that is the clinical endpoint of an inflammatory process and endothelial dysfunction. Study and development of new therapies against cardiovascular disease must be tested in vitro cell models, prior to be evaluated in vivo.To this aim, new cell culture platforms are developed that allow cells to grow and respond to their environment in a realistic manner. In this work, the cell adhesion and morphology of endothelial cells are investigated on functionalized porous silicon substrates with two different pore size configurations: macroporous and nanoporous silicon. Herein, we modified the surfaces of porous silicon substrates by aminopropyl triethoxysilane, and we studied how different pore geometries induced different cellular response in the cell morphology and adhesion. The cell growth over the surface of porous silicon becomes an attractive field, especially for medical applications. Surface properties of the biomaterial are associated with cell adhesion and as well as, with proliferation, migration and differentiation.
Prediction of remission after metabolic surgery using a novel scoring system in type 2 diabetes – a retrospective cohort study
Authors: Ugale Surendra , Gupta Neeraj , Modi Kirtikumar D , Kota Sunil K , Satwalekar Vasisht , Naik Vishwas , Swapna Modukuri , Kumar KVS Hari
Published: August 2014

Background

Remission of diabetes is seen in more than 60% of patients after bariatric surgery. There is extensive variability in the remission rates between different surgical procedures. We analyzed our database and aimed to develop an easy scoring system to predict the probability of diabetes remission after two surgical procedures i.e. Ileal Interposition coupled with Sleeve Gastrectomy (IISG) or Diverted Sleeve Gastrectomy (IIDSG).

Methods

In this retrospective study, we analyzed records pertaining to patients who underwent IISG (n = 46) and IIDSG (n = 29). The primary outcome measure was diabetes remission (A1c <6.5% and not requiring hypoglycemic drugs). We identified seven preoperative clinical variables (age, duration of diabetes, body mass index, micro and macrovascular complications, use of insulin and stimulated C-peptide) based on our previous reports to be included in the diabetes remission score (DRS). The DRS score (7 – 14) was compared between the patients with and without remission in both the surgery groups.

Results

Mean DRS in patients who underwent IISG was 9.2 ± 1.4. Twenty one (46%) had a remission in diabetes. DRS was significantly lower in patients with remission than patients without remission (8.1 ± 0.8 versus 10.2 ± 0.9, p < 0.0001). Mean DRS in patients who underwent IIDSG was 10.4 ± 1.3. Twenty one (72%) had a remission in diabetes. DRS was significantly lower in patients with remission than patients without remission (9.7 ± 0.8 versus 12.0 ± 0.5, p < 0.0001). Patients with a DRS ≥ 10 in IISG group and more than 12 in IIDSG group did not get into remission.

Conclusion

Preoperative DRS can be a useful tool to select the type of surgical procedure and to predict the postoperative diabetes remission.

Trial registration

NCT00834626.
Mesenchymal stem cells, not conditioned medium, contribute to kidney repair after ischemia-reperfusion injury
Authors: Xing Li , Cui Rui , Peng Lei , Ma Jing , Chen Xiao , Xie Ru-Juan , Li Bing
Published: August 2014

Introduction

Studies have shown that stem cells exert their therapeutic effects on acute kidney injury (AKI) through paracrine/endocrine actions. If the protective effect is mediated in an endocrine manner, the injection of the factors that these cells secrete could be effective, but the effect of conditioned medium (CM) remains controversial.

Methods

In this study, we cultured mesenchymal stem cells (MSCs) and then transplanted them into an ischemia-reperfusion (I/R) injury model. CM was also injected into mice, and the histological changes, level of cell proliferation, loss of peritubular capillaries and anti-inflammatory and anti-apoptotic effects were examined at different time points.

Results

The results showed that MSC infusion improved renal function and histological alterations, leading to significantly reduced mortality. MSC administration also promoted kidney microvasculature repair, attenuated kidney peritubular capillary loss, increased the proliferation of parenchymal cells and decreased CD68-positive macrophage infiltration and apoptotic cells. Although we determined that CM contained proangiogenic factors, including hepatocyte growth factor (HGF), vascular endothelial growth factor-A (VEGF-A) and insulin-like growth factor-1 (IGF-1), no favorable effects were observed during the course of repair.

Conclusions

Our data show that MSC infusion promotes kidney repair in a variety of ways, including enhancement of the repair of peritubular capillaries and tubular epithelial cells and anti-inflammatory and anti-apoptotic effects. MSCs can secrete high levels of proangiogenic growth factors, but CM results in a nonsignificant improvement, indicating that MSCs play a role in kidney repair through paracrine rather than endocrine mechanisms. These results indicate that MSC infusion is a promising therapeutic strategy for promoting kidney repair after injury.
New method for estimating gas hydrate saturation in the Shenhu area
Authors: Chen Yajing , Dunn Keh-Jim , Liu Xuewei , Du Manlin , Lei Xiong
Published: August 2014

Accurately predicting the saturation of the gas hydrate is one of the most critical issues for reserves calculation. At present, empirically geologic and physical constraints dependency equations have been developed to estimate hydrate saturation. However, the models derived from the equations are too simplistic to imitate the complicated submarine-sediments system. We have developed a new method for gas hydrate saturation predictions in the Shenhu area of the South China Sea. This method is different from traditional ones. It is dependent on a statistical estimator of data/samplings. The method solves the inverse problem for which a database consisting of pairs of inputs and corresponding outputs is required. This method uses radial-basis-function (RBF) interpolation to derive a nonlinear mapping function between P-wave velocity increment (database input) and gas hydrate saturation (database output). Such a mapping function is then used for predicting the output when input is known in other places. We defined the velocity increment as the amount of actual velocity deviated from background velocity. The parameters of the interpolating function were calibrated using the database. The test results of this method on well SH2 and well SH7 in the Shenhu area were quite satisfying. The RBF interpolation method is a fast and efficient way for gas hydrate saturation prediction, and it allowed us to bypass complicated physical models’ inference.
Application of seismic attributes and spectral decomposition for reservoir characterization of a complex fluvial system: Case study of the Carbonera Formation, Llanos foreland basin, Colombia
Authors: Torrado Lucia , Mann Paul , Bhattacharya Janok
Published: August 2014

Hydrocarbon exploration in the Llanos foreland basin of eastern Colombia has traditionally focused on structural traps. However, in the past decade, the country’s oil demand has generated an increased interest in exploration for stratigraphic traps. We integrated [Formula: see text] of 3D seismic data volumes with eight wells in the Central Llanos area to assess the reservoir potential of the fluvial channel deposits of the Late Eocene–Oligocene Carbonera Formation in the Casanare Province. Distinguishing nonproductive, mud-filled channels from productive sand-filled channels is of economic importance for hydrocarbon exploration because both channel types can exhibit a similar seismic character. Our interpretation of the fluvial sandstone and the reservoir identification was based on 3D seismic attributes, including coherence, curvature, and spectral decomposition, and the analysis of fluvial geomorphology. Analysis of stratal slices through coherence, isofrequency amplitude cubes, and curvature cubes revealed (1) a northeast-trending meandering fluvial system with changes in the rivers’ paleoflow direction from southwest to northeast during the period of the Late Eocene to the Early Miocene, (2) development of prospective sandy point bars, scrolls, and sand bar deposits, and (3) channel ridges and bases accentuated by differential compaction dependent on the channel’s filling material. Based on our attribute analysis, we were able to characterize nonprospective mud-filled channels versus prospective sand-filled channels.
Fast gravity inversion of basement relief
Authors: Silva João B. C. , Santos Darcicléa F. , Gomes Karina P.
Published: August 2014

Gravity interpretation of large sedimentary basins requires a large number of observations and of parameters estimations, so the development of very efficient gravity inversion methods applicable to such environments is of utmost importance. We found that the highly efficient Bott’s method can be cast in the framework of Gauss-Newton’s method for minimizing nonlinear functions. Also, we extended Bott’s method to (1) be applicable to sedimentary basins with density contrast between the sediments and the basement decreasing with depth according to different laws, (2) optimize the modulus of the parameter correction vector, (3) stabilize the solution by imposing that it be smooth, and (4) quit the iteration according to an objective and effective criterion. To keep up the efficiency of Bott’s method, stable solutions were obtained by applying a moving average to the usually unstable solution obtained at the last iteration. Solutions as efficacious as those obtained by the usual nonlinear method were produced by the present extension at a much smaller computation time. Nonlinear methods, with different implementations for solving a linear system of equations, required between one and two orders of magnitude more time to produce similar solutions using between 2000 and 3000 parameters and observations, for example.
LPXRFa, the Piscine Ortholog of GnIH, and LPXRF Receptor Positively Regulate Gonadotropin Secretion in Tilapia (Oreochromis niloticus)
Authors: Biran Jakob , Golan Matan , Mizrahi Naama , Ogawa Satoshi , Parhar Ishwar S. , Levavi-Sivan Berta
Published: August 2014

LPXRFamide (LPXRFa) peptides have been characterized for their ability to inhibit gonadotropin (GTH) release in birds and stimulate growth hormone (GH) release in frogs. However, their involvement in regulating the reproductive hypothalamo-pituitary-gonadal axis in mammals and fish is inconclusive. To study the role of LPXRFa peptides in the regulation of GTH secretion, we cloned tilapia LPXRFa and LPXRF receptor (LPXRF-R). Processing of the tilapia preproLPXRFa liberated three mature LPXRFa peptides that varied in size and post-translational modifications. Phylogenetic analysis of LPXRFa and the closely related RFamide peptide PQRFa showed clear clustering of each peptide sequence with its orthologs from various vertebrates. Signal-transduction analysis of the tilapia LPXRF-R in COS-7 cells showed clear stimulation of CRE-dependent luciferase activity, whereas the human NPFFR1 showed suppression of forskolin-induced CRE-dependent activity in this system. Administration of the tilapia pyroglutaminated LPXRFa-2 peptide to primary cell culture of tilapia pituitaries, or to reproductive female tilapia by ip injection, positively regulated both LH and FSH release in vivo and in vitro. Using double-labeled fluorescent in-situ hybridization and immunofluorescence, βLH cells were found to co-express both tilapia lpxrf and tilapia lpxrf-r mRNA, whereas some of the βFSH cells coexpressed only lpxrf-r mRNA. No coexpression of tilapia lpxrf-r was identified in GH-positive cells. These findings suggest that the LPXRFa system is a potent positive regulator of the reproductive neuroendocrine axis of tilapia.
Changes in RFamide-Related Peptide-1 (RFRP-1)-Immunoreactivity During Postnatal Development and the Estrous Cycle
Authors: Jørgensen Sara R. , Andersen Mille D. , Overgaard Agnete , Mikkelsen Jens D.
Published: August 2014

GnRH is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos-positive RFRP-1-ir neurons was significantly higher in diestrus as compared with proestrus and estrus. In conclusion, we found that adult females, as compared with males, have significantly more RFRP-1-ir per cell, and these cells are regulated during the estrous cycle.
Leptin Resistance Is Not the Primary Cause of Weight Gain Associated With Reduced Sex Hormone Levels in Female Mice
Authors: da Silva Regina P. , Zampieri Thais T. , Pedroso João A.B. , Nagaishi Vanessa S. , Ramos-Lobo Angela M. , Furigo Isadora C. , Câmara Niels O. , Frazão Renata , Donato Jose
Published: August 2014

Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin, and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 d or 24 wk after ovariectomy) but not 7 days after the surgery. In addition, we observed a progressive decrease in the coexpression of LepR and estrogen receptor-α in the hypothalamus after the ovariectomy, resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin-resistance state.
The Use of Protein-DNA, Chromatin Immunoprecipitation, and Transcriptome Arrays to Describe Transcriptional Circuits in the Dehydrated Male Rat Hypothalamus
Authors: Qiu Jing , Kleineidam Anna , Gouraud Sabine , Yao Song Tieng , Greenwood Mingkwan , Hoe See Ziau , Hindmarch Charles , Murphy David
Published: August 2014

The supraoptic nucleus (SON) of the hypothalamus is responsible for maintaining osmotic stability in mammals through its elaboration of the antidiuretic hormone arginine vasopressin. Upon dehydration, the SON undergoes a function-related plasticity, which includes remodeling of morphology, electrical properties, and biosynthetic activity. This process occurs alongside alterations in steady state transcript levels, which might be mediated by changes in the activity of transcription factors. In order to identify which transcription factors might be involved in changing patterns of gene expression, an Affymetrix protein-DNA array analysis was carried out. Nuclear extracts of SON from dehydrated and control male rats were analyzed for binding to the 345 consensus DNA transcription factor binding sequences of the array. Statistical analysis revealed significant changes in binding to 26 consensus elements, of which EMSA confirmed increased binding to signal transducer and activator of transcription (Stat) 1/Stat3, cellular Myelocytomatosis virus-like cellular proto-oncogene (c-Myc)-Myc-associated factor X (Max), and pre-B cell leukemia transcription factor 1 sequences after dehydration. Focusing on c-Myc and Max, we used quantitative PCR to confirm previous transcriptomic analysis that had suggested an increase in c-Myc, but not Max, mRNA levels in the SON after dehydration, and we demonstrated c-Myc- and Max-like immunoreactivities in SON arginine vasopressin-expressing cells. Finally, by comparing new data obtained from Roche-NimbleGen chromatin immunoprecipitation arrays with previously published transcriptomic data, we have identified putative c-Myc target genes whose expression changes in the SON after dehydration. These include known c-Myc targets, such as the Slc7a5 gene, which encodes the L-type amino acid transporter 1, ribosomal protein L24, histone deactylase 2, and the Rat sarcoma proto-oncogene (Ras)-related nuclear GTPase.
Paradise Lostand the Secret of Lucretian Sufficiency
Authors: Ellenzweig Sarah
Published: August 2014

The question of how and why a body falls in Paradise Lost persistently returns to the declining bodies that occupy Lucretius’s De rerum natura. Milton’s Christian support of the Arminian doctrine of free will, his argument that man is “Sufficient to have stood, though free to fall,” thus unfolds in a provocative dialogue with the Lucretian theory of agency. Setting forth a view of matter’s autonomous and vital properties that flirts dangerously with naturalism, Milton emerges as the uneasy inheritor of an ancient and underground Epicurean tradition that understood motion as a self-expressive endeavor of bodies. Moreover, his use of Lucretian physics in Paradise Lost challenges established models of providential superintendence. From Satan to the poem’s speaker to Adam and Eve, this challenge presents itself most enduringly through the Lucretian concept of self-motion, of animate and potentially endless movement independent of external power.
Histone H3.3 regulates dynamic chromatin states during spermatogenesis
Authors: Yuen Benjamin T. K. , Bush Kelly M. , Barrilleaux Bonnie L. , Cotterman Rebecca , Knoepfler Paul S.
Published: August 2014

The histone variant H3.3 is involved in diverse biological processes, including development, transcriptional memory and transcriptional reprogramming, as well as diseases, including most notably malignant brain tumors. Recently, we developed a knockout mouse model for the H3f3b gene, one of two genes encoding H3.3. Here, we show that targeted disruption of H3f3b results in a number of phenotypic abnormalities, including a reduction in H3.3 histone levels, leading to male infertility, as well as abnormal sperm and testes morphology. Additionally, null germ cell populations at specific stages in spermatogenesis, in particular spermatocytes and spermatogonia, exhibited increased rates of apoptosis. Disruption of H3f3b also altered histone post-translational modifications and gene expression in the testes, with the most prominent changes occurring at genes involved in spermatogenesis. Finally, H3f3b null testes also exhibited abnormal germ cell chromatin reorganization and reduced protamine incorporation. Taken together, our studies indicate a major role for H3.3 in spermatogenesis through regulation of chromatin dynamics.
Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a
Authors: Choe Chong Pyo , Crump J. Gage
Published: August 2014

The pharyngeal pouches are a segmental series of epithelial structures that organize the embryonic vertebrate face. In mice and zebrafish that carry mutations in homologs of the DiGeorge syndrome gene TBX1, a lack of pouches correlates with severe craniofacial defects, yet how Tbx1 controls pouch development remains unclear. Using mutant and transgenic rescue experiments in zebrafish, we show that Tbx1 functions in the mesoderm to promote the morphogenesis of pouch-forming endoderm through wnt11r and fgf8a expression. Consistently, compound losses of wnt11r and fgf8a phenocopy tbx1 mutant pouch defects, and mesoderm-specific restoration of Wnt11r and Fgf8a rescues tbx1 mutant pouches. Time-lapse imaging further reveals that Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells. We therefore propose a two-step model in which Tbx1 coordinates the Wnt-dependent epithelial destabilization of pouch-forming cells with their collective migration towards Fgf8a-expressing mesodermal guideposts.
Isolation and Structure of Three Bislactones, Eremopetasitenin B4 and Eremofarfugins F and G, from Ligularia przewalskii and Revision of the Structure of an Epoxy-lactone Isolated from Ligularia intermedia
Authors: Saito Yoshinori , Kamada Aya , Okamoto Yasuko , Gong Xun , Kuroda Chiaki , Tori Motoo
Published: August 2014

Three bislactones belonging to the eremophilane type were isolated from Ligularia przewalskii (Asteraceae): an epoxy-lactone (eremopetasitenin B4) identical to the previously isolated lactone, whose structure was revised in this work; a new enol-lactone (eremofarfugin F); and its diastereoisomer at C-11 (eremofarfugin G). This was identical to the reported lactone, whose stereochemistry was left undetermined. The stereochemistry along with the NMR data of this diastereoisomer was assigned in this study.
IRBIS: a systematic search for conserved complementarity
Authors: Pervouchine Dmitri D.
Published: August 2014

IRBIS is a computational pipeline for detecting conserved complementary regions in unaligned orthologous sequences. Unlike other methods, it follows the “first-fold-then-align” principle in which all possible combinations of complementary k-mers are searched for simultaneous conservation. The novel trimming procedure reduces the size of the search space and improves the performance to the point where large-scale analyses of intra- and intermolecular RNA–RNA interactions become possible. In this article, I provide a rigorous description of the method, benchmarking on simulated and real data, and a set of stringent predictions of intramolecular RNA structure in placental mammals, drosophilids, and nematodes. I discuss two particular cases of long-range RNA structures that are likely to have a causal effect on single- and multiple-exon skipping, one in the mammalian gene Dystonin and the other in the insect gene Ca-α1D. In Dystonin, one of the two complementary boxes contains a binding site of Rbfox protein similar to one recently described in Enah gene. I also report that snoRNAs and long noncoding RNAs (lncRNAs) have a high capacity of base-pairing to introns of protein-coding genes, suggesting possible involvement of these transcripts in splicing regulation. I also find that conserved sequences that occur equally likely on both strands of DNA (e.g., transcription factor binding sites) contribute strongly to the false-discovery rate and, therefore, would confound every such analysis. IRBIS is an open-source software that is available at http://genome.crg.es/~dmitri/irbis/.
Pancreatic Cancer: Insights from Counterterrorism Theories
Authors: McGuire Mary F.
Published: August 2014

Recently, a molecular tumor profile analyzed at our medical institution evoked an uncommon communications hub in one of the molecular pathway networks. The patient was a multiyear survivor of pancreatic cancer, and the oncologist requested molecular analyses that would assist in treatment decisions. The hub was noticed because of its topological similarity to optimal terrorist networks that are resilient against attack. Although the hub's topology could have been simply a methodological artifact, its presence did support the consulting pathologist's recommendation that the oncologist refrain from overstimulating the patient's active immune system. In addition, the terrorism/cancer analogy sparked investigation into environments that neutralize covert networks; this led to novel hypotheses about cancer prevention and control for further research. Despite parallels between the “war on cancer” and the “war on terrorism,” there has been very little crossover work between biomedical researchers and researchers in military intelligence. Here is an example of how analytical methods based on infrastructure similarities between molecular interaction pathways and terrorism networks support preclinical research and medical decision making for diseases that have progressed beyond standard-of-care treatments.
Parameter Estimation: The Proper Way to Use Bayesian Posterior Processes with Brownian Noise
Authors: Cohen Asaf
Published: August 2014

This paper studies a problem of Bayesian parameter estimation for a sequence of scaled counting processes whose weak limit is a Brownian motion with an unknown drift. The main result of the paper is that the limit of the posterior distribution processes is, in general, not equal to the posterior distribution process of the mentioned Brownian motion with the unknown drift. Instead, it is equal to the posterior distribution process associated with a Brownian motion with the same unknown drift and a different standard deviation coefficient. The difference between the two standard deviation coefficients can be arbitrarily large. The characterization of the limit of the posterior distribution processes is then applied to a family of stopping time problems. We show that the proper way to find asymptotically optimal solutions to stopping time problems, with respect to the scaled counting processes, is by looking at the limit of the posterior distribution processes rather than by the naive approach of looking at the limit of the scaled counting processes themselves. The difference between the performances can be arbitrarily large.
Exact Analysis of Capacitated Two-Echelon Inventory Systems with Priorities
Authors: Abouee-Mehrizi Hossein , Baron Opher , Berman Oded
Published: August 2014

We consider a two-echelon inventory system with a capacitated centralized production facility and several distribution centers (DCs). Both production and transportation times are stochastic with general distributions. Demand arrives at each DC according to an independent Poisson process and is backlogged if the DC is out of stock. We allow different holding and backlog costs at the different DCs. We assume that inventory at DCs is managed using the one-for-one replenishment policy. The main objective of this paper is to investigate the control of the multiechelon M/G/1 setting with general transportation times. To achieve this objective, we analyze several decentralized allocation policies including the first-come, first-served (FCFS), strict priority (SP), and multilevel rationing (MR) policies. For our analytic results, we assume no order crossing. We derive the cost function for a capacitated two-echelon inventory system with general transportation times under these policies. Our numerical examples show that the FCFS policy may outperform the MR policy, even though the latter has been shown to be better in the centralized setting. This suggests that in decentralized settings there is a need to focus on policies that prioritize customers when there is backlog. This focus is in contrast to the centralized settings, where inventory rationing policies that focus on prioritization when there is available inventory are effective. We therefore introduce and analyze the generalized multilevel rationing (GMR) priority policy. We compare the GMR policy with other policies and show that the GMR policy outperforms the three policies used in the centralized setting. We also compare the GMR policy with the myopic (T), longest queue first (LQF), and the optimal (when order crossing is allowed during the transportation time) policies. Our results show that when the uncertainty of the transportation times is low, the GMR policy outperforms the myopic (T) and LQF policies and that the gap between the optimal policy and the GMR policy is not high.
New Aspects of Progesterone Interactions with the Actin Cytoskeleton and Neurosteroidogenesis in the Cerebellum and the Neuronal Growth Cone
Authors: Wessel Lisa , Olbrich Laura , Brand-Saberi Beate , Theiss Carsten
Published: August 2014

The impact of progesterone on neuronal tissues in the central (CNS) and peripheral (PNS) nervous system is of significant scientific and therapeutic interest. Glial and neuronal cells of vertebrates express steroidogenic enzymes, and are able to synthesize progesterone de novo from cholesterol. Progesterone is described to have neuroprotective, neuroreparative, anti-degenerative, and anti-apoptotic effects in the CNS and the PNS. Thus, the first clinical studies promise new therapeutic options using progesterone in the treatment of patients with traumatic brain injury. Additionally, experimental data from different animal models suggest further positive effects of progesterone on neurological diseases such as cerebral ischemia, peripheral nerve injury and amyothropic lateral sclerosis. In regard to this future clinical use of progesterone, we discuss in this review the underlying physiological principles of progesterone effects in neuronal tissues. Mechanisms leading to morphological reorganizations of neurons in the CNS and PNS affected by progesterone are addressed, with special focus on the actin cytoskeleton. Furthermore, new aspects of a progesterone-dependent regulation of neurosteroidogenesis mediated by the recently described progesterone binding protein PGRMC1 in the nervous system are discussed.
Simulation of geosynthetic load–strain–time behaviour by the non-linear three-component model
Authors: Kongkitkul W. , Chantachot T. , Tatsuoka F.
Published: August 2014

ABSTRACT: Polymer geosynthetic reinforcement materials exhibit significant elasto-visco-plastic load–strain behaviour that is controlled by, at least, current strain rate. For this reason, it is not possible to accurately evaluate the tensile load history only from a given tensile strain in a physical model test in the laboratory or with a full-scale soil structure in the field. A non-linear three-component model that can realistically simulate rate-dependent load–strain behaviour of polymer geosynthetic reinforcement is described with detailed explanations of the model framework together with the constitutive equations. The algorithms to simulate behaviours in three basic modes, constant strain rate monotonic loading, creep loading and load relaxation, are presented. A working example in Microsoft Excel with a user-defined Microsoft Visual Basic source code is provided in the appendices (which are available as supplementary data on the ICE Virtual Library website) so that readers can readily use the model.
Negatively buoyant jets at low Froude numbers in a co-flow
Authors: Hajikandi Hooman , Barjastehmaleki Shayan
Published: August 2014

Experiments on inclined negatively buoyant jets discharging at low densimetric Froude numbers into a co-flow were carried out. The spread of the jet was observed by flow visualisation techniques. The results include three length scales of the jet's trajectory: the maximum penetration depth, the horizontal distance from the source to the locus of maximum penetration depth and the horizontal length from the source to the impact point. Empirical equations that express dimensionless geometrical length scales of the jet in terms of the densimetric Froude number, velocity ratio and angles of inclination were derived. The maximum penetration depth occurred at vertical discharges, whereas the maximum horizontal distance from the source to the impact point and the maximum trajectory length were obtained at 45° and 60° inclinations, respectively. The results were applied to the diffusion of inclined negatively buoyant jets in shallow water streams.
Impact of an Intensive Lifestyle Intervention on Use and Cost of Medical Services Among Overweight and Obese Adults With Type 2 Diabetes: The Action for Health in Diabetes
Authors: Espeland Mark A. , Glick Henry A. , Bertoni Alain , Brancati Frederick L. , Bray George A. , Clark Jeanne M. , Curtis Jeffrey M. , Egan Caitlin , Evans Mary , Foreyt John P. , Ghazarian Siran , Gregg Edward W. , Hazuda Helen P. , Hill James O. , Hire Don , Horton Edward S. , Hubbard Van S. , Jakicic John M. , Jeffery Robert W. , Johnson Karen C. , Kahn Steven E. , Killean Tina , Kitabchi Abbas E. , Knowler William C. , Kriska Andrea , Lewis Cora E. , Miller Marsha , Montez Maria G. , Murillo Anne , Nathan David M. , Nyenwe Ebenezer , Patricio Jennifer , Peters Anne L. , Pi-Sunyer Xavier , Pownall Henry , Redmon J. Bruce , Rushing Julia , Ryan Donna H. , Safford Monika , Tsai Adam G. , Wadden Thomas A. , Wing Rena R. , Yanovski Susan Z. , Zhang Ping
Published: August 2014

OBJECTIVE

To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial.

RESEARCH DESIGN AND METHODS

A total of 5,121 overweight or obese adults with type 2 diabetes were randomly assigned to an ILI that promoted weight loss or to a comparison condition of diabetes support and education (DSE). Use and costs of health-care services were recorded across an average of 10 years.

RESULTS

ILI led to reductions in annual hospitalizations (11%, P = 0.004), hospital days (15%, P = 0.01), and number of medications (6%, P < 0.001), resulting in cost savings for hospitalization (10%, P = 0.04) and medication (7%, P < 0.001). ILI produced a mean relative per-person 10-year cost savings of $5,280 (95% CI 3,385–7,175); however, these were not evident among individuals with a history of cardiovascular disease.

CONCLUSIONS

Compared with DSE over 10 years, ILI participants had fewer hospitalizations, fewer medications, and lower health-care costs.
A test of common assumptions used to infer subglacial water flow through overdeepenings
Authors: Dow Christine F. , Kavanaugh Jeffrey L. , Sanders Johnny W. , Cuffey Kurt M.
Published: August 2014

Borehole instrument records from a cirque glacier with an overdeepened bed are examined to assess the validity of widely held glacial hydrological assumptions. At this glacier, hydraulic-potential calculations suggest water below overburden pressure will flow into the overdeepening, where the steepness of the riegel causes water to pool in the basin and increase in pressure. Our subglacial water pressure data also show high consistent pressures in the overdeepening and the presence of an active, variable-pressure drainage system towards the margin of the cirque. Therefore, we find that although uniform hydraulic-potential calculations are not directly applicable, they can still be useful for interpretation of the subglacial hydrological system. We also examine supercooling assumptions under different pressure and temperature regimes for water flowing over a riegel, driven using our borehole records of subglacial water temperatures that are consistently above the pressure-melting point during the late melt season. Our results show that even a slight increase in basal temperatures relative to the local pressure-melting point is sufficient to prevent a reduction in basal hydraulic conductivity as a result of supercooling freeze-on.
Do No Harm: A Cross-Disciplinary, Cross-Cultural Climate Ethics
Authors: Rentmeester Casey
Published: August 2014

Anthropogenic climate change has become a hot button issue in the scientific, economic, political, and ethical sectors. While the science behind climate change is clear, responses in the economic and political realms have been unfulfilling. On the economic front, companies have marketed themselves as pioneers in the quest to go green while simultaneously engaging in environmentally destructive practices and on the political front, politicians have failed to make any significant global progress. I argue that climate change needs to be framed as an ethical issue to make serious progress towards the path to a sustainable human civilization. In an effort to motivate the urgency needed to confront climate change, I argue that climate change seriously affects human beings living here and now, and if one cares about unnecessarily harming fellow innocent living human beings, then one should care about one’s own environmental impact related to climate change. Since this argument does not depend upon any specific philosophical, religious, or ethical tradition but applies regardless of one’s particular background, I hope to induce genuine concern among all human beings regarding this issue.
Some New Results on the Multiple-AccessWiretap Channel
Authors: Dai Bin , Ma Zheng
Published: August 2014

In this paper, some new results on the multiple-access wiretap channel (MAC-WT) are provided. Specifically, first, we investigate the degraded MAC-WT, where two users transmit their corresponding confidential messages (no common message) to a legitimate receiver via a multiple-access channel (MAC), while a wiretapper wishes to obtain the messages via a physically degraded wiretap channel. The secrecy capacity region of this model is determined for both the discrete memoryless and Gaussian cases. For the Gaussian case, we find that this secrecy capacity region is exactly the same as the achievable secrecy rate region provided by Tekin and Yener, i.e., Tekin–Yener’s achievable region is exactly the secrecy capacity region of the degraded Gaussian MAC-WT. Second, we study a special Gaussian MAC-WT, and find the power control for two kinds of optimal points (max-min point and single user point) on the secrecy rate region of this special Gaussian model.
Dynamic Feedforward Control of a Diesel Engine Based on Optimal Transient Compensation Maps
Authors: Mancini Giorgio , Asprion Jonas , Cavina Nicolò , Onder Christopher , Guzzella Lino
Published: August 2014

To satisfy the increasingly stringent emission regulations and a demand for an ever lower fuel consumption, diesel engines have become complex systems with many interacting actuators. As a consequence, these requirements are pushing control and calibration to their limits. The calibration procedure nowadays is still based mainly on engineering experience, which results in a highly iterative process to derive a complete engine calibration. Moreover, automatic tools are available only for stationary operation, to obtain control maps that are optimal with respect to some predefined objective function. Therefore, the exploitation of any leftover potential during transient operation is crucial. This paper proposes an approach to derive a transient feedforward (FF) control system in an automated way. It relies on optimal control theory to solve a dynamic optimization problem for fast transients. A partially physics-based model is thereby used to replace the engine. From the optimal solutions, the relevant information is extracted and stored in maps spanned by the engine speed and the torque gradient. These maps complement the static control maps by accounting for the dynamic behavior of the engine. The procedure is implemented on a real engine and experimental results are presented along with the development of the methodology.
Artificial Intelligence in Public Health Prevention of Legionelosis in Drinking Water Systems
Authors: Sinčak Peter , Ondo Jaroslav , Kaposztasova Daniela , Virčikova Maria , Vranayova Zuzana , Sabol Jakub
Published: August 2014

Good quality water supplies and safe sanitation in urban areas are a big challenge for governments throughout the world. Providing adequate water quality is a basic requirement for our lives. The colony forming units of the bacterium Legionella pneumophila in potable water represent a big problem which cannot be overlooked for health protection reasons. We analysed several methods to program a virtual hot water tank with AI (artificial intelligence) tools including neuro-fuzzy systems as a precaution against legionelosis. The main goal of this paper is to present research which simulates the temperature profile in the water tank. This research presents a tool for a water management system to simulate conditions which are able to prevent legionelosis outbreaks in a water system. The challenge is to create a virtual water tank simulator including the water environment which can simulate a situation which is common in building water distribution systems. The key feature of the presented system is its adaptation to any hot water tank. While respecting the basic parameters of hot water, a water supplier and building maintainer are required to ensure the predefined quality and water temperature at each sampling site and avoid the growth of Legionella. The presented system is one small contribution how to overcome a situation when legionelosis could find good conditions to spread and jeopardize human lives.
Adoptive Immunotherapy Strategies with Cytokine-Induced Killer (CIK) Cells in the Treatment of Hematological Malignancies
Authors: Schmeel Frederic , Schmeel Leonard , Gast Sanna-Marie , Schmidt-Wolf Ingo
Published: August 2014

Cytokine-induced killer (CIK) cells are a heterogeneous population of immune effector cells that feature a mixed T- and Natural killer (NK) cell-like phenotype in their terminally-differentiated CD3+CD56+ subset. The easy availability, high proliferation rate and widely major histocompatibility complex (MHC)-unrestricted antitumor activity of CIK cells contribute to their particularly advantageous profile, making them an attractive approach for adoptive immunotherapy. CIK cells have shown considerable cytotoxicity against both solid tumors and hematological malignancies in vitro and in animal studies. Recently, initial clinical experiences demonstrated the feasibility and efficacy of CIK cell immunotherapy in cancer patients, even at advanced disease stages. Likewise, the clinical application of CIK cells in combination with standard therapeutic procedures revealed synergistic antitumor effects. In this report, we will focus our consideration on CIK cells in the treatment of hematological malignancies. We will give insight into the latest advances and future perspectives and outline the most prominent results obtained in 17 clinical studies. Overall, CIK cells demonstrated a crucial impact on the treatment of patients with hematological malignancies, as evidenced by complete remissions, prolonged survival durations and improved quality of life. However, up to now, the optimal application schedule eventually favoring their integration into clinical practice has still to be developed.