bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cyborg Astrobiologist: matching of prior textures by image compression for geological mapping and novelty detection
Authors: McGuire P.C. , Bonnici A. , Bruner K.R. , Gross C. , Ormö J. , Smosna R.A. , Walter S. , Wendt L. 
Published: February 2014

AbstractWe describe an image-comparison technique of Heidemann and Ritter (2008a, b), which uses image compression, and is capable of: (i) detecting novel textures in a series of images, as well as of: (ii) alerting the user to the similarity of a new image to a previously observed texture. This image-comparison technique has been implemented and tested using our Astrobiology Phone-cam system, which employs Bluetooth communication to send images to a local laptop server in the field for the image-compression analysis. We tested the system in a field site displaying a heterogeneous suite of sandstones, limestones, mudstones and coal beds. Some of the rocks are partly covered with lichen. The image-matching procedure of this system performed very well with data obtained through our field test, grouping all images of yellow lichens together and grouping all images of a coal bed together, and giving 91% accuracy for similarity detection. Such similarity detection could be employed to make maps of different geological units. The novelty-detection performance of our system was also rather good (64% accuracy). Such novelty detection may become valuable in searching for new geological units, which could be of astrobiological interest. The current system is not directly intended for mapping and novelty detection of a second field site based on image-compression analysis of an image database from a first field site, although our current system could be further developed towards this end. Furthermore, the image-comparison technique is an unsupervised technique that is not capable of directly classifying an image as containing a particular geological feature; labelling of such geological features is donepost factoby human geologists associated with this study, for the purpose of analysing the system's performance. By providing more advanced capabilities for similarity detection and novelty detection, this image-compression technique could be useful in giving more scientific autonomy to robotic planetary rovers, and in assisting human astronauts in their geological exploration and assessment.
Evaluating Systems Pharmacology Models Is Different From Evaluating Standard Pharmacokinetic–Pharmacodynamic Models
Authors: Agoram B 
Published: February 2014

Based on the author's recent experience, there appears to be some confusion regarding the steps required to qualify a systems pharmacology model as adequate for the intended purpose. This manuscript outlines the model evaluation approach used in the author's recent publication1 on the systems pharmacology of a 5‐lipoxygenase inhibitor and is an attempt to generate discussion on this topic within the pharmacometrics and systems pharmacology community.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e101; doi:10.1038/psp.2013.77; published online 19 February 2014
Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine
Authors: Heuberger Julian , Kosel Frauke , Qi Jingjing , Grossmann Katja S. , Rajewsky Klaus , Birchmeier Walter 
Published: February 2014

Significance
The mammalian intestine is covered by an extended villus epithelium that contains absorptive enterocytes and secretory cell types that are replenished from stem cells in the lower parts of crypts. Signals that control stem cells are known, but those that regulate differentiation of secretory lineages are less well understood. Here we used mouse genetics and intestinal organoid cultures to characterize the intricate signaling networks in the crypts that regulate the choice between secretory goblet and paneth cells and stem cells. MAPK suppression in the crypts increases Wnt/β-catenin signaling and promotes paneth and stem cells. High MAPK signals in the crypts decreases paneth cells and stem cells and favors goblet cell properties. Mechanistically, MAPK regulates Wnt/β-catenin signaling on the posttranslational level.
Equitability, mutual information, and the maximal information coefficient
Authors: Kinney Justin B. , Atwal Gurinder S. 
Published: February 2014

Significance
Attention has recently focused on a basic yet unresolved problem in statistics: How can one quantify the strength of a statistical association between two variables without bias for relationships of a specific form? Here we propose a way of mathematically formalizing this “equitability” criterion, using core concepts from information theory. This criterion is naturally satisfied by a fundamental information-theoretic measure of dependence called “mutual information.” By contrast, a recently introduced dependence measure called the “maximal information coefficient” is seen to violate equitability. We conclude that estimating mutual information provides a natural and practical method for equitably quantifying associations in large datasets.
Small distances can keep bacteria at bay for days
Authors: van Bunnik Bram A. D. , Ssematimba Amos , Hagenaars Thomas J. , Nodelijk Gonnie , Haverkate Manon R. , Bonten Marc J. M. , Hayden Mary K. , Weinstein Robert A. , Bootsma Martin C. J. , De Jong Mart C. M. 
Published: February 2014

Significance
The failure to identify avoidable contacts makes indirect transmission the prime cause of difficulties in controlling epidemic spread (e.g., bacteria in hospitals, livestock infections). Our results from tailored indirect transmission experiments show that there is a clear delay in onset of transmission when there is a small distance between sender and recipient, and that this delay differs considerably between bacterium species. We showed that the observed patterns can, as we understand it, only be explained by taking into account the slow (random) transport of infectious material from sender to recipient and mortality of the bacterium during that transport. The implication of this is that hygiene measures can influence indirect transmission as shown for an antibiotic-resistance bacterium in a hospital.
A dynamically assembled cell wall synthesis machinery buffers cell growth
Authors: Lee Timothy K. , Tropini Carolina , Hsin Jen , Desmarais Samantha M. , Ursell Tristan S. , Gong Enhao , Gitai Zemer , Monds Russell D. , Huang Kerwyn Casey 
Published: February 2014

Significance
For complex biological processes, the formation of protein complexes is a strategy for coordinating the activities of many enzymes in space and time. It has been hypothesized that growth of the bacterial cell wall involves stable synthetic complexes, but neither the existence of such complexes nor the consequences of such a mechanism for growth efficiency have been demonstrated. Here, we use single-molecule tracking to demonstrate that the association between an essential cell wall synthesis enzyme and the cytoskeleton is highly dynamic, which allows the cell to buffer growth rate against large fluctuations in enzyme abundance. This indicates that dynamic association can be an efficient strategy for coordination of multiple enzymes, especially those for which excess abundance can be harmful to cells.
OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation
Authors: Singleton Rachelle S. , Liu-Yi Phebee , Formenti Fabio , Ge Wei , Sekirnik Rok , Fischer Roman , Adam Julie , Pollard Patrick J. , Wolf Alexander , Thalhammer Armin , Loenarz Christoph , Flashman Emily , Yamamoto Atsushi , Coleman Mathew L. , Kessler Benedikt M. , Wappner Pablo , Schofield Christopher J. , Ratcliffe Peter J. , Cockman Matthew E. 
Published: February 2014

Significance
Members of the 2-oxoglutarate (2OG)-dependent oxygenase superfamily catalyze a range of important biological oxidations. Structurally informed bioinformatic predictions suggest that the human genome encodes as yet unassigned members of the superfamily. We describe work demonstrating that 2OG and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1) is a protein hydroxylase that modifies the small ribosomal subunit protein RPS23 at a conserved prolyl residue in the ribosome-decoding center and that suppression or deletion of OGFOD1 is associated with the activation of translational stress pathways. Together with studies of homologous genes in flies and yeast described in accompanying manuscripts, the work identifies a unique function for 2OG oxygenase-catalyzed hydroxylation in ribosome biology.
Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange
Authors: Burns Michael C. , Sun Qi , Daniels R. Nathan , Camper DeMarco , Kennedy J. Phillip , Phan Jason , Olejniczak Edward T. , Lee Taekyu , Waterson Alex G. , Rossanese Olivia W. , Fesik Stephen W. 
Published: February 2014

Significance
Ras is one of the most highly validated targets in cancer; however, the discovery of potent inhibitors of Ras has been difficult to achieve. We report the discovery of small molecules that bind to a pocket on the Ras:Son of Sevenless:Ras complex and alter Ras activity in biochemical and cell-based experiments. High-resolution cocrystal structures define the protein–ligand interactions, and the lead compounds provide a starting point for the discovery of potent inhibitors of Ras signaling.
Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB
Authors: Colavin Alexandre , Hsin Jen , Huang Kerwyn Casey 
Published: February 2014

Significance
Cytoskeletal filaments drive many dynamic cellular processes, such as the regulation of shape by actin networks in eukaryotes and by the actin homolog MreB in rod-shaped bacteria. Here, we use all-atom molecular dynamics simulations to demonstrate close parallels between the conformational dynamics of actin and MreB, in which polymerization induces flattening of MreB subunits that restructures the ATP binding pocket to promote hydrolysis. We also find that ATP-bound MreB filaments are substantially more curved than ADP-bound filaments, and this bending is highly correlated with the degree of flattening of the subunits. Our results provide molecular-scale insight into the diverse structural states of MreB during its assembly process, revealing properties that may be general to the broad actin family.
Mossy fiber-evoked subthreshold responses induce timing-dependent plasticity at hippocampal CA3 recurrent synapses
Authors: Brandalise Federico , Gerber Urs 
Published: February 2014

Significance
Dentate mossy fibers represent the main conduit for information transfer from the cerebral cortex to the hippocampus, a structure essential for learning and memory. It is generally accepted that the information conveyed by mossy fibers must take the form of powerful all-or-none digital signals, known as action potentials, to ensure the formation of stable memory traces; however, experiments in behaving rodents have revealed that mossy fibers might not generate sufficient numbers of action potentials in hippocampal cells to support memory function. Here we show that analog signals elicited by mossy fiber activity, which are weaker but much more frequent than action potentials, can compensate for the paucity of digital signaling and effectively control hippocampal circuits important for memory.
Compartmentalized cyanophycin metabolism in the diazotrophic filaments of a heterocyst-forming cyanobacterium
Authors: Burnat Mireia , Herrero Antonia , Flores Enrique 
Published: February 2014

Significance
The heterocyst-forming cyanobacteria represent a true multicellular system found in the bacterial world that adds unique features to biodiversity. They grow as chains of cells containing two metabolically interdependent cellular types, the vegetative cells that fix carbon dioxide performing oxygenic photosynthesis and the dinitrogen-fixing heterocysts. Heterocysts accumulate a cell inclusion, cyanophycin [multi-L-arginyl-poly (L-aspartic acid)], as a nitrogen reservoir. We have found that the second enzyme of cyanophycin catabolism, isoaspartyl dipeptidase, is present at significantly higher levels in vegetative cells than in heterocysts, identifying the nitrogen-rich dipeptide β-aspartyl-arginine as a nitrogen vehicle to the vegetative cells and showing that compartmentalization of a catabolic route is used to improve the physiology of nitrogen fixation.
Liquid metal enabled pump
Authors: Tang Shi-Yang , Khoshmanesh Khashayar , Sivan Vijay , Petersen Phred , O’Mullane Anthony P. , Abbott Derek , Mitchell Arnan , Kalantar-zadeh Kourosh 
Published: February 2014

Significance
The utilization of small-scale pumps is presently hampered by their limited flow rates with respect to the input power or their rather complicated fabrication process. These issues arise as many conventional pumping effects rely on moving elements. Here, we demonstrate the concept of a liquid metal enabled pump with no mechanical parts by simply incorporating droplets of Galinstan. The liquid metal enabled pump creates high flow rates (>5,000 µL/min) at exceptionally low powers (<15 mW) by electrowetting/deelectrowetting the surface upon application of electric field. The presented pump is both efficient and simple; hence, it has the potential to advance the field of actuation in small-scale systems.
Evolutionary history and metabolic insights of ancient mammalian uricases
Authors: Kratzer James T. , Lanaspa Miguel A. , Murphy Michael N. , Cicerchi Christina , Graves Christina L. , Tipton Peter A. , Ortlund Eric A. , Johnson Richard J. , Gaucher Eric A. 
Published: February 2014

Significance
Human susceptibility to gout is driven by the fact that we have a pseudogene for uricase that prevents a functional enzyme from being produced. Our inability to convert highly insoluble uric acid into a more soluble molecule makes us vulnerable to disease and other health complications. We have exploited ancestral sequence reconstruction to better understand how and why apes lost this functional enzyme. Our ancient proteins support one hypothesis that the progressive loss of uricase activity allowed our ancestors to readily accumulate fat via the metabolism of fructose from fruits. This adaptation may have provided our ancestors with an advantage when the energy-rich rainforests of Europe and Asia were displaced by temperate forests by the end of the Oligocene.
IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans
Authors: de Luca Antonella , Smeekens Sanne P. , Casagrande Andrea , Iannitti Rossana , Conway Kara L. , Gresnigt Mark. S. , Begun Jakob , Plantinga Theo S. , Joosten Leo A. B. , van der Meer Jos W. M. , Chamilos Georgios , Netea Mihai G. , Xavier Ramnik J. , Dinarello Charles A. , Romani Luigina , van de Veerdonk Frank L. 
Published: February 2014

Significance
Chronic granulomatous disease (CGD) has an immunodeficiency component and, in addition, an autoinflammatory component in which autophagy and inflammasome activation are linked and amenable to IL-1 blockade. This study provides a rationale to perform clinical trials to investigate the efficacy of blocking IL-1 in CGD colitis and expands the therapeutic potential of IL-1 antagonists to inflammatory diseases with defective autophagy.
Form, function, and evolution of living organisms
Authors: Banavar Jayanth R. , Cooke Todd J. , Rinaldo Andrea , Maritan Amos 
Published: February 2014

Significance
Understanding the origin and evolution of the shapes observed in nature remains an exciting challenge. Even from a cursory inspection, it is clear that the shapes of animals and plants, as determined by the distribution of mass over volume, are distinct. Animals are able to move and are approximately homogeneous in their mass distribution. Plants are rooted organisms endowed with heterogeneous self-similar geometry where the mass is concentrated in the stem and branches rather than in the leaves. By addressing the fundamental physics underlying the relation between form and physiology and the origins of Kleiber’s law, we discuss how the two divergent life forms of plants and animals may have independently evolved to achieve equivalent energetic efficiencies.
Structural motif of polyglutamine amyloid fibrils discerned with mixed-isotope infrared spectroscopy
Authors: Buchanan Lauren E. , Carr Joshua K. , Fluitt Aaron M. , Hoganson Andrew J. , Moran Sean D. , de Pablo Juan J. , Skinner James L. , Zanni Martin T. 
Published: February 2014

Significance
Expanded polyglutamine (polyQ) tracts in proteins are associated with many neurodegenerative diseases, including Huntington disease. The structure and dynamics of polyQ peptides are difficult to study due to the homogenous nature of the sequence and their high propensity to aggregate into amyloid fibrils. In this manuscript, we study mixtures of isotope-labeled peptides with 2D IR spectroscopy to resolve the structure of individual monomers within the polyQ. These results, in combination with spectra calculated from molecular-dynamics simulations, determine the dominant structure of polyQ fibrils consists of stacked β-hairpins.
Transcription factors IIS and IIF enhance transcription efficiency by differentially modifying RNA polymerase pausing dynamics
Authors: Ishibashi Toyotaka , Dangkulwanich Manchuta , Coello Yves , Lionberger Troy A. , Lubkowska Lucyna , Ponticelli Alfred S. , Kashlev Mikhail , Bustamante Carlos 
Published: February 2014

Significance
Regulation of gene expression controls fundamental cellular processes, such as growth and differentiation. Gene expression begins at transcription, in which the eukaryotic RNA polymerase (Pol II) synthesizes the precursors of mRNA during the elongation phase. The speed and fidelity of the process are regulated by many transcription elongation factors, including transcription factors IIS (TFIIS) and IIF (TFIIF), which directly interact with the enzyme. Using a single-molecule optical-tweezers assay, we have quantified the effects of these factors on the dynamics of transcription elongation by Pol II on both bare and nucleosomal DNA. We showed that TFIIF mainly prevents Pol II from pause entering, whereas TFIIS assists with pause recovery, and quantitatively described these effects on the kinetics of transcription elongation by Pol II.
Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model
Authors: Siopi Maria , Mavridou Eleftheria , Mouton Johan W. , Verweij Paul E. , Zerva Loukia , Meletiadis Joseph 
Published: February 2014

Abstract

Background
Although voriconazole reached the bedside 10 years ago and became the standard care in the treatment of invasive aspergillosis, reliable clinical breakpoints are still in high demand. Moreover, this has increased due to the recent emergence of azole resistance.

Methods
Four clinical wild-type and non-wild-type A. fumigatus isolates with voriconazole CLSI MICs in the range of 0.125–2 mg/L were tested in an in vitro pharmacokinetic (PK)/pharmacodynamic (PD) model. Mouse PK was simulated and in vitro data were compared with in vivo outcome. Human PK was simulated and susceptibility breakpoints and trough levels required for optimal treatment were determined for the CLSI and EUCAST methods after 48 h and the gradient concentration MIC test strip (MTS) method after 24 h using the in vitro PK/PD relationship and Monte Carlo simulation.

Results
The in vitro PK/PD target (95% CI) associated with 50% of the maximal antifungal activity (EC50) was 28.61 (16.18–50.61), close to the in vivo EC50 of 14.67 (9.31–21.58) fAUC0–24/CLSI MIC. When human PK was simulated, the EC50 was 24.7 (17.9–35.6) fAUC0–12/CLSI MIC and it was associated with 6 week survival in clinical studies of invasive pulmonary aspergillosis. Target attainment rates were ≤5% (0%–24%), 42% (16%–58%), 68% (54%–75%) and ≥79% (73%–86%) for isolates with CLSI MICs ≥2, 1, 0.5 and ≤0.25 mg/L, respectively. A trough/CLSI MIC ratio of 2 was required for optimal treatment. The susceptible/intermediate/resistant breakpoints were determined to be 0.25/0.5–1/2 mg/L for CLSI, 0.5/1–2/4 mg/L for EUCAST and 0.25/0.375–1/1.5 mg/L for MTS.

Conclusions
These susceptibility breakpoints and target values for therapeutic drug monitoring could be used to optimize voriconazole therapy against A. fumigatus.
Ferritin and LIC
Authors: Smith Erika , Lebensburger Jeffrey , Hilliard Lee , Kelly David , Fineberg Naomi , Bai Shuting , Howard Tom 
Published: February 2014

ABSTRACTObjective:Chronic blood transfusion therapy reduces clinical events in children with sickle cell anemia but increases risk for an iron‐related liver injury. Liver biopsy is the gold standard technique for quantifying liver iron content (LIC) and evaluating liver pathology. Ferritin, liver enzymes, and R2* magnetic resonance imaging of the liver are obtained as surrogate markers. In this study we compared surrogate markers with the gold standard, liver biopsy, in assessing liver histology.Methods:We conducted a retrospective review of 259 liver biopsies in 109 children with sickle cell anemia on chronic transfusion therapy and chelation therapy during a 9‐year period at a single center. Liver pathology was compared with LIC, ferritin, and alanine aminotransferase.Results:Ferritin correlates with LIC (r = 0.74, P < 0.001), although there is a broad range of ferritin values for a given LIC. Furthermore, patients with a high LIC (≥7 mg Fe/g dry weight) demonstrated significantly higher ferritin as compared to the patients with lower LIC <7 (P < 0.001). Periportal/portal inflammation also showed a significant relation. There was no significance when comparing ferritin and lobular inflammation or ferritin and alanine aminotransferase. When evaluating LIC in relation to fibrosis, the present study revealed that there was only a significant correlation with severe fibrosis (F = 36, P < 0.001).Conclusions:The results suggest that although correlations exist among ferritin and LIC and severe fibrosis and LIC, caution should be taken when they are used in isolation. Liver biopsy provides important pathologic information that cannot be obtained through surrogate markers.
Objective Assessment of Swallow Function in Children With Suspected Aspiration Using Pharyngeal Automated Impedance Manometry
Authors: Rommel Nathalie , Selleslagh Margot , Hoffman Ilse , Smet Maria H. , Davidson Geoffrey , Tack Jan , Omari Taher Imad 
Published: February 2014

ABSTRACTObjectives:The purpose of the present study was to apply a new method, pharyngeal automated impedance manometry (AIM), as an objective assessment tool of swallow function relevant to aspiration, in a cohort of paediatric patients with dysphagia.Methods:We studied 20 children (mean age 6 years [5 months to 13.4 years]) referred for videofluoroscopy to assess aspiration risk with simultaneous manometry–impedance. Fluoroscopic evidence of aspiration was scored using a validated aspiration–penetration score. Pressure–flow profiles were analysed using AIM analysis measuring peak pressure, pressure at nadir impedance, time from nadir impedance to peak pressure, and flow interval. These variables were combined into a swallow risk index (SRI).Results:Six of 20 children presented with deglutitive aspiration during videofluoroscopic assessment of swallowing. Of 58 liquid swallows analysed, in 9 aspiration was observed. Multiple logistic regression identified longer flow interval (P < 0.05), higher SRI (P < 0.05) and increased pressure in the upper oesophageal sphincter during maximal bolus flow (P < 0.05) to be the dominant risk variables predictive of aspiration in children. Each of these nonradiologically derived pressure–flow variables correlated with higher aspiration scores on videofluoroscopy (P < 0.01).Conclusions:We present novel, preliminary findings in children with deglutitive aspiration, suggesting that pharyngeal AIM can detect alterations in pressure–flow characteristics of swallowing that predispose to aspiration risk.