bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostics of Inherited Bleeding Disorders of Secondary Hemostasis: An Easy Guide for Routine Clinical Laboratories
Authors: Lippi Giuseppe , Franchini Massimo , Favaloro Emmanuel
Published: April 2016

The investigation of inherited bleeding disorders of secondary hemostasis remains a challenge for most clinical laboratories, especially those that lack experience or specialized personnel. Bleeding can be essentially caused by a variety of acquired or congenital conditions, which impair either primary or secondary hemostasis. Since a universally agreed approach for the diagnostics of hemorrhagic disorders is still unavailable, this article aims to provide an easy guidance for routine clinical laboratories. This pragmatic approach to identifying and diagnosing inherited bleeding disorders of secondary hemostasis entails a multifaceted strategy, based on a collection of personal and family history, the results of first-line tests, which can then be followed by second- or third-line analyses to definitely establish the specific nature and the severity of the bleeding phenotype. Briefly, the presence of profound hemorrhages rather than mucocutaneous bleeding is suggestive of a disorder of secondary hemostasis. Although a positive family history is frequently reported in patients with congenital conditions, the lack of clinically meaningful symptoms in patient's relatives is not absolutely indicative of an acquired disorder. The next step encompasses the assessment of first-line coagulation tests (i.e., prothrombin time, activated partial thromboplastin time, and fibrinogen) if family history is not suggestive of a specific factor deficiency. The emergence of abnormal data of these assays and the variable combination of their results is then helpful to guide the performance of second-line tests, in particular specific factor assays, which will then provide a reasonable basis for a preliminary diagnosis. Third-line tests (namely, immunological assays of clotting factors and molecular biology) are then supportive for a final diagnosis and for identifying the nature of the factor deficiency (i.e., quantitative or functional).
Kommunale Antwort auf die Privaten
Authors: Mau Jens
Published: April 2016

Steffen Grebner, Chef des Klinikums Ernst von Bergmann, will in Brandenburg eine Kette kommunaler Kliniken gründen, und so den Umsatz seines Unternehmens in den nächsten fünf Jahren von 250 auf 500 Millionen Euro verdoppeln. Im kma Interview erklärt Grebner, wie er dies bewerkstelligen wird.
Faible für fiese Themen
Authors: Gaede Kirsten
Published: April 2016

Im Jubiläumsjahr der kma stellen wir Ihnen an dieser Stelle jedes Mal einen unserer freien Mitarbeiter vor.
Das große Glück, zwei Kulturen zu kennen
Authors: Sickinger Nina
Published: April 2016

Sowohl in Deutschland als auch in meiner Heimat Afghanistan ist der Umgang mit Patienten sehr durch Höflichkeit geprägt. Einen Unterschied sehe ich jedoch bei der Aufklärung.
Comparative melting and healing of B-DNA and Z-DNA by an infrared laser pulse
Authors: Man Viet Hoang , Pan Feng , Sagui Celeste , Roland Christopher
Published: April 2016

We explore the use of a fast laser melting simulation approach combined with atomistic molecular dynamics simulations in order to determine the melting and healing responses of B-DNA and Z-DNA dodecamers with the same d(5′-CGCGCGCGCGCG-3′)2 sequence. The frequency of the laser pulse is specifically tuned to disrupt Watson-Crick hydrogen bonds, thus inducing melting of the DNA duplexes. Subsequently, the structures relax and partially refold, depending on the field strength. In addition to the inherent interest of the nonequilibrium melting process, we propose that fast melting by an infrared laser pulse could be used as a technique for a fast comparison of relative stabilities of same-sequence oligonucleotides with different secondary structures with full atomistic detail of the structures and solvent. This could be particularly useful for nonstandard secondary structures involving non-canonical base pairs, mismatches, etc.
Successful network inference from time-series data using mutual information rate
Authors: Bianco-Martinez E. , Rubido N. , Antonopoulos Ch. G. , Baptista M. S.
Published: April 2016

This work uses an information-based methodology to infer the connectivity of complex systems from observed time-series data. We first derive analytically an expression for the Mutual Information Rate (MIR), namely, the amount of information exchanged per unit of time, that can be used to estimate the MIR between two finite-length low-resolution noisy time-series, and then apply it after a proper normalization for the identification of the connectivity structure of small networks of interacting dynamical systems. In particular, we show that our methodology successfully infers the connectivity for heterogeneous networks, different time-series lengths or coupling strengths, and even in the presence of additive noise. Finally, we show that our methodology based on MIR successfully infers the connectivity of networks composed of nodes with different time-scale dynamics, where inference based on Mutual Information fails.
Defect formation in graphene during low-energy ion bombardment
Authors: Ahlberg P. , Johansson F. O. L. , Zhang Z.-B. , Jansson U. , Zhang S.-L. , Lindblad A. , Nyberg T.
Published: April 2016

This letter reports on a systematic investigation of sputter induced damage in graphene caused by low energy Ar+ ion bombardment. The integral numbers of ions per area (dose) as well as their energies are varied in the range of a few eV’s up to 200 eV. The defects in the graphene are correlated to the dose/energy and different mechanisms for the defect formation are presented. The energetic bombardment associated with the conventional sputter deposition process is typically in the investigated energy range. However, during sputter deposition on graphene, the energetic particle bombardment potentially disrupts the crystallinity and consequently deteriorates its properties. One purpose with the present study is therefore to demonstrate the limits and possibilities with sputter deposition of thin films on graphene and to identify energy levels necessary to obtain defect free graphene during the sputter deposition process. Another purpose is to disclose the fundamental mechanisms responsible for defect formation in graphene for the studied energy range.
Intermittency, coherent structures and dissipation in plasma turbulence
Authors: Wan M. , Matthaeus W. H. , Roytershteyn V. , Parashar T. N. , Wu P. , Karimabadi H.
Published: April 2016

Collisionless dissipation in turbulent plasmas such as the solar wind and the solar corona has been an intensively studied subject recently, with new insights often emerging from numerical simulation. Here we report results from high resolution, fully kinetic simulations of plasma turbulence in both two (2D) and three (3D) dimensions, studying the relationship between intermittency and dissipation. The simulations show development of turbulent coherent structures, characterized by sheet-like current density structures spanning a range of scales. An approximate dissipation measure is employed, based on work done by the electromagnetic field in the local electron fluid frame. This surrogate dissipation measure is highly concentrated in small subvolumes in both 2D and 3D simulations. Fully kinetic simulations are also compared with magnetohydrodynamics (MHD) simulations in terms of coherent structures and dissipation. The interesting result emerges that the conditional averages of dissipation measure scale very similarly with normalized current density J in 2D and 3D particle-in-cell and in MHD. To the extent that the surrogate dissipation measure is accurate, this result implies that on average dissipation scales as ∼J2 in turbulent kinetic plasma. Multifractal intermittency is seen in the inertial range in both 2D and 3D, but at scales ∼ion inertial length, the scaling is closer to monofractal.
A noniterative asymmetric triple excitation correction for the density-fitted coupled-cluster singles and doubles method: Preliminary applications
Authors: Bozkaya Uğur
Published: April 2016

An efficient implementation of the asymmetric triples correction for the coupled-cluster singles and doubles [ΛCCSD(T)] method [S. A. Kucharski and R. J. Bartlett, J. Chem. Phys. 108, 5243 (1998); T. D. Crawford and J. F. Stanton, Int. J. Quantum Chem. 70, 601 (1998)] with the density-fitting [DF-ΛCCSD(T)] approach is presented. The computational time for the DF-ΛCCSD(T) method is compared with that of ΛCCSD(T). Our results demonstrate that the DF-ΛCCSD(T) method provide substantially lower computational costs than ΛCCSD(T). Further application results show that the ΛCCSD(T) and DF-ΛCCSD(T) methods are very beneficial for the study of single bond breaking problems as well as noncovalent interactions and transition states. We conclude that ΛCCSD(T) and DF-ΛCCSD(T) are very promising for the study of challenging chemical systems, where the coupled-cluster singles and doubles with perturbative triples method fails.
The free energy of the metastable supersaturated vapor via restricted ensemble simulations. III. An extension to the Corti and Debenedetti subcell constraint algorithm
Authors: Nie Chu , Geng Jun , Marlow William H.
Published: April 2016

In order to improve the sampling of restricted microstates in our previous work [C. Nie, J. Geng, and W. H. Marlow, J. Chem. Phys. 127, 154505 (2007); 128, 234310 (2008)] and quantitatively predict thermal properties of supersaturated vapors, an extension is made to the Corti and Debenedetti subcell constraint algorithm [D. S. Corti and P. Debenedetti, Chem. Eng. Sci. 49, 2717 (1994)], which restricts the maximum allowed local density at any point in a simulation box. The maximum allowed local density at a point in a simulation box is defined by the maximum number of particles Nm allowed to appear inside a sphere of radius R, with this point as the center of the sphere. Both Nm and R serve as extra thermodynamic variables for maintaining a certain degree of spatial homogeneity in a supersaturated system. In a restricted canonical ensemble, at a given temperature and an overall density, series of local minima on the Helmholtz free energy surface F(Nm, R) are found subject to different (Nm, R) pairs. The true equilibrium metastable state is identified through the analysis of the formation free energies of Stillinger clusters of various sizes obtained from these restricted states. The simulation results of a supersaturated Lennard-Jones vapor at reduced temperature 0.7 including the vapor pressure isotherm, formation free energies of critical nuclei, and chemical potential differences are presented and analyzed. In addition, with slight modifications, the current algorithm can be applied to computing thermal properties of superheated liquids.
Mechanisms for the formation of thymine under astrophysical conditions and implications for the origin of life
Authors: Bera Partha P. , Nuevo Michel , Materese Christopher K. , Sandford Scott A. , Lee Timothy J.
Published: April 2016

Nucleobases are the carriers of the genetic information in ribonucleic acid and deoxyribonucleic acid (DNA) for all life on Earth. Their presence in meteorites clearly indicates that compounds of biological importance can form via non-biological processes in extraterrestrial environments. Recent experimental studies have shown that the pyrimidine-based nucleobases uracil and cytosine can be easily formed from the ultraviolet irradiation of pyrimidine in H2O-rich ice mixtures that simulate astrophysical processes. In contrast, thymine, which is found only in DNA, is more difficult to form under the same experimental conditions, as its formation usually requires a higher photon dose. Earlier quantum chemical studies confirmed that the reaction pathways were favorable provided that several H2O molecules surrounded the reactants. However, the present quantum chemical study shows that the formation of thymine is limited because of the inefficiency of the methylation of pyrimidine and its oxidized derivatives in an H2O ice, as supported by the laboratory studies. Our results constrain the formation of thymine in astrophysical environments and thus the inventory of organic molecules delivered to the early Earth and have implications for the role of thymine and DNA in the origin of life.
On the generalized Buckley-Leverett equation
Authors: Burczak Jan , Granero-Belinchón Rafael , Luli Garving K.
Published: April 2016

In this paper we study the generalized Buckley-Leverett equation with nonlocal regularizing terms. One of these regularizing terms is diffusive, while the other one is conservative. We prove that if the regularizing terms have order higher than one (combined), there exists a global strong solution for arbitrarily large initial data. In the case where the regularizing terms have combined order one, we prove the global existence of solution under some size restriction for the initial data. Moreover, in the case where the conservative regularizing term vanishes, regardless of the order of the diffusion and under a certain hypothesis on the initial data, we also prove the global existence of a strong solution, and we obtain some new entropy balances. Finally, we provide numerics suggesting that, if the order of the diffusion is 0 < α < 1, a finite time blow up of the solution is possible.
Spontaneous wrinkling of soft matter by energetic deposition of Cr and Au
Authors: Teixeira F. S. , Araújo W. W. R. , Salvadori M. C.
Published: April 2016

Wrinkling of stiff thin films deposited on compliant substrates is an effect that has been broadly investigated. However, wrinkling consequent to metal ion implantation has been less studied. In the work described here, we have explored the sub-micron wrinkling phenomena that spontaneously occur when metal ions (Au and Cr) are implanted with energy of a few tens of electron volts (49 eV for Au and 72 eV for Cr) into a compliant material (PDMS). This very low energy ion implantation was performed using a Filtered Cathodic Vacuum Arc technique, a process often referred to as energetic deposition or energetic condensation. For comparison, Au and Cr depositions with similar doses were also done using a sputtering technique (with lower particle energy of approximately 2 eV), and no wrinkle formation was then observed. In this way, we can discuss the role of ion energy in wrinkle formation. Depth profiles of the implanted material were calculated using the Tridyn computer simulation code for each metal, for several implantation doses. UV-vis absorption spectroscopy analysis confirmed the presence of metal nanoparticles. Atomic Force Microscopy imaging with spectral processing was used to compare the wrinkle morphology for each case investigated.
All-optical tunable on-chip plasmon-induced transparency based on two surface-plasmon-polaritons absorption
Authors: Chai Zhen , Hu Xiaoyong , Yang Hong , Gong Qihuang
Published: April 2016

All-optical tunable on-chip plasmon-induced transparency is realized in integrated plasmonic circuits based on two surface-plasmon-polaritons absorption induced polymerization of SU-8 photoresist. Owing to the enhanced interaction between surface plasmon polaritons and SU-8 guaranteed by the slow light effect around the transparency window and the strong light confinement effect of the plasmonic nanocavity modes, a continuous shift range of 24 nm in the central wavelength of the transparency window was obtained. The threshold power of the two surface-plasmon-polaritons absorption induced polymerization of SU-8 was as low as 100 μW, which is three orders of magnitude less than previous reports.
Note: Expanding the bandwidth of the ultra-low current amplifier using an artificial negative capacitor
Authors: Xie Kai , Liu Yan , Li XiaoPing , Guo Lixin , Zhang Hanlu
Published: April 2016

The bandwidth and low noise characteristics are often contradictory in ultra-low current amplifier, because an inevitable parasitic capacitance is paralleled with the high value feedback resistor. In order to expand the amplifier’s bandwidth, a novel approach was proposed by introducing an artificial negative capacitor to cancel the parasitic capacitance. The theory of the negative capacitance and the performance of the improved amplifier circuit with the negative capacitor are presented in this manuscript. The test was conducted by modifying an ultra-low current amplifier with a trans-impedance gain of 50 GΩ. The results show that the maximum bandwidth was expanded from 18.7 Hz to 3.3 kHz with more than 150 times of increase when the parasitic capacitance (∼0.17 pF) was cancelled. Meanwhile, the rise time decreased from 18.7 ms to 0.26 ms with no overshot. Any desired bandwidth or rise time within these ranges can be obtained by adjusting the ratio of cancellation of the parasitic and negative capacitance. This approach is especially suitable for the demand of rapid response to weak current, such as transient ion-beam detector, mass spectrometry analysis, and fast scanning microscope.
A simple electrokinetic protein preconcentrator utilizing nano-interstices
Authors: Chen Yu-Hung , Wu Hsuan Franziska , Amstislavskaya Tamara G. , Li Chang-Yu , Jen Chun-Ping
Published: April 2016

This work proposes a simple method for creating nanofluidic channels for protein preconcentration through self-assembled gold nanoparticles (AuNPs) using the exclusion-enrichment effect. A depletion force is elicited in nano-interstices among self-assembled AuNPs due to the overlap of electrical double layers (EDLs); therefore, proteins quickly accumulate. The experimental results show that the generation of depletion forces is correlated with the size of the AuNPs. The self-assembled monolayer of AuNPs (13 nm in diameter) can successfully preconcentrate proteins through effective EDL overlapping. This approach provides a new process to produce nanochannels that does not require high-voltage or time-consuming fabrication.
Amino Acid Functional Polymers: Biomimetic Polymer Design Enabling Catalysis, Chiral Materials, and Drug Delivery
Authors: Brisson Emma R. L. , Xiao Zeyun , Connal Luke A.
Published: April 2016

Amino acids are the natural building blocks for the world around us. Highly functional, these small molecules have unique catalytic properties, chirality, and biocompatibility. Imparting these properties to surfaces and other macromolecules is highly sought after and represents a fast-growing field. Polymers functionalized with amino acids in the side chains have tunable optical properties, pH responsiveness, biocompatibility, structure and self-assembly properties. Herein, we review the synthesis of amino acid functional polymers, discuss manipulation of available strategies to achieve the desired responsive materials, and summarize some exciting applications in catalysis, chiral particles, and drug delivery.
Restoring dissolved organic carbon subsidies from floodplains to lowland river food webs: a role for environmental flows?
Authors: Baldwin Darren S. , Colloff Matthew J. , Mitrovic Simon M. , Bond Nick R. , Wolfenden Ben
Published: April 2016

Environmental flows are managed events in river systems designed to enhance the ecological condition of aquatic ecosystems. Although not traditionally seen as important in lowland rivers, there is mounting evidence that terrestrial subsidies can be an important energy source in aquatic metazoan food webs. We argue that the apparent lack of importance of terrestrial subsidies to many lowland river food webs may reflect an artefact resulting from historical anthropogenic changes to lowland river–floodplain ecosystems, including the loss of lateral connectivity between rivers and their floodplains, changes in floodplain land use and carbon stores, and loss of sites of transformation within the main channel. The loss of floodplain subsidies to the main river channel can be partially redressed using environmental flows; however, this will require mimicking important aspects of natural high-flow events that have hitherto been overlooked when targeting environmental flows to a limited suite of biota. We suggest that key biotic targets for environmental flow releases may not be achievable unless river–floodplain subsidies are sufficiently restored. Environmental flows can go some way to addressing this shortfall, but only if floodplain subsidies to river channels are explicitly included in the design and management of environmental flows.
Applicability of the photogrammetry technique to determine the volume and the bulk density of small soil aggregates
Authors: Moret-Fernández D. , Latorre B. , Peña C. , González-Cebollada C. , López M. V.
Published: April 2016

Aggregate density (ρ) is defined as the relationship between the mass and the volume occupied by an aggregate. Previous studies have characterised ρ on large to medium-sized soil aggregates (>4 mm diameter); however, little information is available for smaller aggregates (<4 mm). The objective of this study was to test the viability of the photogrammetry (PHM) technique to determine the volume and subsequent ρ of small soil aggregates (1–8 mm diameter). The method uses a standard digital camera that photographs a rotating aggregate and reconstructs its three-dimensional surface and the corresponding volume. To validate the method, the volume estimated with PHM on rough stones of different sizes (1–16 mm diameter) was compared with the corresponding volume measured by the Archimedes’ principle. The method was tested on soil aggregates 1–8 mm in diameter, collected from two sites under conventional and conservation tillage treatments. The strong correlation (R2 > 0.99, P < 0.0001) between the volumes estimated on rough stones with the PHM and Archimedes methods demonstrates that this technique can be satisfactorily used to estimate the volume and, consequently, the ρ of small soil aggregates. The results showed an increase in ρ with decreasing aggregate size. A general trend of increasing ρ with the degree of soil disturbance by tillage was also observed.
Internal and external components of the bacterial flagellar motor rotate as a unit
Authors: Hosu Basarab G. , Nathan Vedavalli S. J. , Berg Howard C.
Published: April 2016

Significance

Intracellular components of the bacterial flagellar motor acted on by force-generating elements of the stator to power rotation of the extracellular hook and filament have been visualized by EM. Their molecular composition is known, but their actual rotation has never been shown. Here, a method for bleaching and probing a fusion protein rigidly linked to one of the innermost components of the flagellar motor of
Escherichia coli
, FliN, was used to show that the components commonly thought to rotate as a unit actually do so.
In cellulo phosphorylation induces pharmacological reprogramming of maurocalcin, a cell-penetrating venom peptide
Authors: Ronjat Michel , Feng Wei , Dardevet Lucie , Dong Yao , Al Khoury Sawsan , Chatelain Franck C. , Vialla Virginie , Chahboun Samir , Lesage Florian , Darbon Hervé , Pessah Isaac N. , De Waard Michel
Published: April 2016

Significance

Animal toxin peptides typically exhibit high affinity and selectivity for specific subclasses of cell receptors that account for their activity. Posttranslational modifications of toxin sequences may occur in the venom gland machinery, but there is no example so far of toxins being subjected to such modifications ex situ after delivery to target cells. Here, we provide evidence that the cell permeant maurocalcin (MCa), found in scorpion venom, undergoes PKA-mediated phosphorylation in cellulo, and that posttranslational modification leads to its complete pharmacological reprogramming activity toward ryanodine receptor type 1 (RyR1), a key player in Ca
2+
homeostasis in excitable cells. Phosphorylation converts MCa from a potent stabilizer of RyR1 channel substates to a negative allosteric modulator that mitigates RyR1 channel Ca
2+
leak.
Heterozygous colon cancer-associated mutations of
SAMHD1
have functional significance
Authors: Rentoft Matilda , Lindell Kristoffer , Tran Phong , Chabes Anna Lena , Buckland Robert J. , Watt Danielle L. , Marjavaara Lisette , Nilsson Anna Karin , Melin Beatrice , Trygg Johan , Johansson Erik , Chabes Andrei
Published: April 2016

Significance

The three major DNA replication fidelity determinants are nucleotide selectivity, proofreading, and mismatch repair. Defects in the two latter determinants are now firmly associated with cancer. Nucleotide selectivity is affected by changes in the absolute or relative concentrations of dNTPs. Here, we show that hemizygous
SAMHD1
+/−
mouse embryos have increased dNTP pools compared with wild-type controls and that heterozygous mutations that inactivate SAMHD1 are frequently found in colon cancers. We infer that such cancer cells have increased dNTP pools and, therefore, higher mutation rates. These observations suggest that changes in dNTP concentrations, which affect nucleotide selectivity, the first major determinant of DNA replication fidelity, are associated with cancer.
Short and long-lasting behavioral consequences of agonistic encounters between male
Drosophila melanogaster
Authors: Trannoy Séverine , Penn Jill , Lucey Kenia , Popovic David , Kravitz Edward A.
Published: April 2016

Significance

Animals must adapt to constantly changing environments, defend themselves against predators, and protect mates and territories. Learning and memory are key elements to the adaptations made for survival.
Drosophila
have been favorite study animals for identifying the genes and brain regions involved in learning and memory under a variety of associative and social learning paradigms. Here, we explore an uncharacterized social learning paradigm related to aggression and the consequences of winning and losing bouts. We demonstrate that short- and long-term memories are associated with agonistic encounters, with the memory of defeat lasting longer than the memory of victory. These are first steps in examining the genetic and environmental cues that participate in the development of social memories.
Reproductive trade-offs in extant hunter-gatherers suggest adaptive mechanism for the Neolithic expansion
Authors: Page Abigail E. , Viguier Sylvain , Dyble Mark , Smith Daniel , Chaudhary Nikhil , Salali Gul Deniz , Thompson James , Vinicius Lucio , Mace Ruth , Migliano Andrea Bamberg
Published: April 2016

Significance

The rise of agriculture during the Neolithic period has paradoxically been associated with worldwide population growth despite increases in disease and mortality. We examine the effects of sedentarization and cultivation on disease load, mortality, and fertility among Agta foragers. We report increased disease and mortality rates associated with sedentarization alongside an even larger increase in fertility associated with both participation in cultivation and sedentarization. Thus, mothers who transition to agriculture have higher reproductive fitness. We provide the first empirical evidence, to our knowledge, of an adaptive mechanism behind the expansion of agriculture, explaining how we can reconcile the Neolithic increase in morbidity and mortality with the observed demographic expansion.
Prestimulus influences on auditory perception from sensory representations and decision processes
Authors: Kayser Stephanie J. , McNair Steven W. , Kayser Christoph
Published: April 2016

Significance

The likelihood of perceiving a faint stimulus depends not only on the stimulus itself but also on the state of rhythmic brain activity preceding the stimulus. Previous neuroimaging results did not confirm this state dependency as arising from early sensory representations or later decision-related computations. We show that state affects perception via two mechanisms: one where the amplitude of slow-wave activity influences the scaling of early sensory evidence, and another where the time profile of the activity influences sensory decisions in areas governing cognitive processes. These findings reconcile the plethora of previous findings and delineate two relevant mechanisms.
Soluble guanylate cyclase as an alternative target for bronchodilator therapy in asthma
Authors: Ghosh Arnab , Koziol-White Cynthia J. , Asosingh Kewal , Cheng Georgina , Ruple Lisa , Groneberg Dieter , Friebe Andreas , Comhair Suzy A. A. , Stasch Johannes-Peter , Panettieri Reynold A. , Aronica Mark A. , Erzurum Serpil C. , Stuehr Dennis J.
Published: April 2016

Significance

Asthmatics depend on β-agonist bronchodilator drugs, but a majority develop resistance to these drugs in their lifetime, and new ways to bronchodilate are needed. We show that brochodilation can be triggered in normal human and asthmatic mouse airways through an alternative signaling pathway, using new pharmacologic agents that directly activate the soluble guanylate cyclase (sGC) enzyme. Because an sGC-based drug was recently approved to treat pulmonary arterial hypertension, our findings imply that such drugs could become new bronchodilators in asthma. Our work also provides insight on how the sGC signaling enzyme becomes desensitized toward NO in inflammatory asthma, and thus helps to explain why NO is an ineffective bronchodilator in this disease.
Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics
Authors: Sparrow Janet R.
Published: April 2016

Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation.
Apicomplexa
-specific tRip facilitates import of exogenous tRNAs into malaria parasites
Authors: Bour Tania , Mahmoudi Nassira , Kapps Delphine , Thiberge Sabine , Bargieri Daniel , Ménard Robert , Frugier Magali
Published: April 2016

Significance

We identified a membrane protein that is unique to
Plasmodium
(malaria-causing parasite) and its phylogenetic family members. This protein is localized at the parasite’s surface, binds transfer RNAs (tRNAs) specifically, and directs the import of exogenous tRNAs into the parasite. In the absence of this protein, the parasite’s development is severely reduced. We propose that
Plasmodium
diverts tRNAs from host cells to support its life cycle and discuss the biological pertinence of this unprecedented host–pathogen interaction, as well as the possible fate of imported tRNAs.
Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood
Authors: Klocke Katrin , Sakaguchi Shimon , Holmdahl Rikard , Wing Kajsa
Published: April 2016

Significance

Cytotoxic T lymphocyte antigen-4 (CTLA-4), up-regulated by activated conventional T cells and constitutively expressed by Foxp3+regulatory T cells, is essential for immunological self-tolerance. Because of early fatality in germ-line CTLA-4–deficient mice, the role in adulthood remains unclear. We abrogated CTLA-4 expression in adult mice and compared their phenotype with congenitally CTLA-4–deleted mice. We found that the two modes of CTLA-4 deficiency differed in resulting autoimmune disease phenotype and severity. Additionally, although CTLA-4–deficient mice had more severe collagen-induced arthritis, they were protected against peptide-induced experimental autoimmune encephalomyelitis (EAE). However, onset of protein-induced EAE was only delayed. These results taken together indicate that CTLA-4 deficiency affects both central and peripheral tolerance and Treg cell-mediated suppression.
Nucleotide excision repair by dual incisions in plants
Authors: Canturk Fazile , Karaman Muhammet , Selby Christopher P. , Kemp Michael G. , Kulaksiz-Erkmen Gulnihal , Hu Jinchuan , Li Wentao , Lindsey-Boltz Laura A. , Sancar Aziz
Published: April 2016

Significance

UV wavelengths of sunlight cause damage to genomic DNA in all organisms, including plants. Although UV photoproducts are known to be removed from DNA through the process of nucleotide excision repair in a wide variety of organisms, ranging from bacteria to humans, the mechanism of this repair process in plants has never been examined. Here, using a highly sensitive DNA repair assay that we developed to monitor UV photoproduct repair in vivo, we found that plants remove UV photoproducts from their genomic DNA through a dual-incision mechanism that is nearly identical to that of humans and other eukaryotes.
Final report of APMP.QM-S6: clenbuterol in porcine meat
Authors: Sin D W -M , Ho C , Yip Y -C
Published: April 2016

At the CCQM Organic Analysis Working Group (OAWG) Meeting held in April 2012 and the APMP TCQM Meeting held in November 2012, an APMP supplementary comparison (APMP.QM-S6) on the determination of clenbuterol in porcine meat was supported by the OAWG and APMP TCQM. This comparison was organized by the Government Laboratory, Hong Kong. In order to accommodate a wider participation, a pilot study (APMP.QM-P22) was run in parallel to APMP.QM-S6.

This study provided the means for assessing the measurement capabilities for determination of low-polarity measurands in a procedure that requires extraction, clean-up, analytical separation, and selective detection in a food matrix. A total of 7 institutes registered for the supplementary comparison and 6 of them submitted their results. 4 results were included for SCRV calculation. All participating laboratories applied Isotope Dilution Liquid Chromatography-Tandem Mass Spectrometry (ID-LCMS/MS) technique with clenbuterol-d9 as internal standard spiked for quantitation in this programme.

KEY WORDS FOR SEARCH

APMP.QM-S6 and Clenbuterol

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
ProtPOS: a python package for the prediction of protein preferred orientation on a surface
Authors: Ngai Jimmy C. F. , Mak Pui-In , Siu Shirley W. I.
Published: April 2016

Summary: Atomistic molecular dynamics simulation is a promising technique to investigate the energetics and dynamics in the protein–surface adsorption process which is of high relevance to modern biotechnological applications. To increase the chance of success in simulating the adsorption process, favorable orientations of the protein at the surface must be determined. Here, we present ProtPOS which is a lightweight and easy-to-use python package that can predict low-energy protein orientations on a surface of interest. It combines a fast conformational sampling algorithm with the energy calculation of GROMACS. The advantage of ProtPOS is it allows users to select any force fields suitable for the system at hand and provide structural output readily available for further simulation studies.

Availability and Implementation: ProtPOS is freely available for academic and non-profit uses at http://cbbio.cis.umac.mo/software/protpos

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact: shirleysiu@umac.mo
A design of experiments approach to validation sampling for logistic regression modeling with error-prone medical records
Authors: Ouyang Liwen , Apley Daniel W , Mehrotra Sanjay
Published: April 2016

Background and Objective Electronic medical record (EMR) databases offer significant potential for developing clinical hypotheses and identifying disease risk associations by fitting statistical models that capture the relationship between a binary response variable and a set of predictor variables that represent clinical, phenotypical, and demographic data for the patient. However, EMR response data may be error prone for a variety of reasons. Performing a manual chart review to validate data accuracy is time consuming, which limits the number of chart reviews in a large database. The authors’ objective is to develop a new design-of-experiments–based systematic chart validation and review (DSCVR) approach that is more powerful than the random validation sampling used in existing approaches.

Methods The DSCVR approach judiciously and efficiently selects the cases to validate (i.e., validate whether the response values are correct for those cases) for maximum information content, based only on their predictor variable values. The final predictive model will be fit using only the validation sample, ignoring the remainder of the unvalidated and unreliable error-prone data. A Fisher information based D-optimality criterion is used, and an algorithm for optimizing it is developed.

Results The authors’ method is tested in a simulation comparison that is based on a sudden cardiac arrest case study with 23 041 patients’ records. This DSCVR approach, using the Fisher information based D-optimality criterion, results in a fitted model with much better predictive performance, as measured by the receiver operating characteristic curve and the accuracy in predicting whether a patient will experience the event, than a model fitted using a random validation sample.

Conclusions The simulation comparisons demonstrate that this DSCVR approach can produce predictive models that are significantly better than those produced from random validation sampling, especially when the event rate is low.
Wet soils affect habitat selection of a solitary subterranean rodent (Ctenomys minutus) in a Neotropical region
Authors: Galiano Daniel , Kubiak Bruno B. , Menezes Luciana S. , Overbeck Gerhard E. , de Freitas Thales Renato O.
Published: April 2016

Subterranean rodents are characterized by limited individual mobility and patchy distribution of local populations. Habitat patches where the species is absent may either be unoccupied, but suitable patches, or in fact unsuitable as habitat due to specific habitat features. In the coastal plain of southern Brazil, Ctenomys minutus (Ctenomyidae) inhabits sandy grasslands and dunes. The aim of our study was to analyze the relationship between the distribution of this subterranean rodent and its environment. We considered vegetation and soil features. Our results showed that habitat occupancy patterns of C. minutus are determined by soil moisture and vegetation (food supply), but there might be other habitat features that regulate the habitat choice of this mammal. Habitat discontinuities in the coastal plain of southern Brazil, with numerous barriers to dispersal, are responsible for restricting individuals to their natal areas. This might result in increased intraspecific competition within each population and, consequently, in inbreeding.

Os roedores subterrâneos são caracterizados pela baixa mobilidade dos indivíduos e por apresentarem populações distribuídas em manchas de habitat. As manchas em que os indivíduos estão ausentes podem ser locais desocupados, porém que apresentam condições adequadas para a ocupação, ou de fato serem locais inadequados devido a algumas características ambientais específicas. Na planície costeira do sul do Brasil, a espécie Ctenomys minutus (Ctenomyidae) habita regiões de campos arenosos e dunas costeiras. O objetivo do presente estudo foi analisar a relação entre a distribuição deste roedor subterrâneo e o ambiente em que ele habita. Para tal, consideramos características da vegetação e do solo. Nossos resultados demonstraram que o padrão de ocupação de C. minutus é determinado pela umidade do solo e vegetação (recurso alimentar), mas podem existir outras características que regulam a escolha do habitat deste mamífero. As descontinuidades de habitat na planície costeira do sul do Brasil, com inúmeras barreiras para a dispersão da espécie, são responsáveis por restringir os indivíduos as suas áreas natais. Isso pode resultar no aumento da competição intra-específica dentro das populações e, consequentemente, na endogamia.
Race Characterization of Puccinia striiformis f. sp. tritici, the Cause of Wheat Stripe Rust, in Saskatchewan and Southern Alberta, Canada and Virulence Comparison with Races from the United States
Authors: Brar G. S. , Kutcher H. R.
Published: April 2016

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici, has been common across Saskatchewan, Canada since 2000. Fifty-nine isolates of P. striiformis f. sp. tritici, the majority of which were collected between 2011 and 2013 from Saskatchewan and southern Alberta, were analyzed for virulence frequency and diversity and compared with isolates characterized in the Pacific Northwest and Great Plains regions of the United States. In all, 31 wheat differentials, including 20 near-isogenic lines and 1 triticale variety, differentiated 59 P. striiformis f. sp. tritici isolates into 33 races, of which one race, C-PST-1, represented 31% of the isolates. None of the races were virulent on Yr5, Yr15, or YrSP. Virulence frequency ranged from 65 to 98% on YrA, Yr2, Yr8, Yr9, Yr27, Yr29, Yr32, YrSu, ‘Heines VII’, and ‘Nord Deprez’. Race C-PST-6 was virulent on the greatest number of the differentials (n = 25) and C-PST-18 on the fewest (n = 14). Discriminant analysis of principal components and multivariate cluster analyses detected three and four major groups, respectively, which differed from each other in terms of virulence spectrum and year of collection. The diversity of the P. striiformis f. sp. tritici population in southern Alberta was greater than in Saskatchewan, which indicated that, although P. striiformis f. sp. tritici is primarily windborne over great distances and does not usually overwinter, there are detectable differences in virulence between these regions of western Canada. Comparative analyses of virulence frequency of Saskatchewan or southern Alberta isolates with isolates representing races from the Great Plains and the Pacific Northwest of the United States indicated greater similarity of Saskatchewan races to the Great Plains despite strong correlations with both parts of the United States. This suggests that the P. striiformis f. sp. tritici population in Saskatchewan is a mixture of inoculum from both parts of the United States.
Coevolutionary Dynamics of Rice Blast Resistance GenePi-taandMagnaporthe oryzaeAvirulence GeneAVR-Pita 1
Authors: Jia Yulin , Zhou Erxun , Lee Seonghee , Bianco Tracy
Published: April 2016

The Pi-ta gene in rice is effective in preventing infections by Magnaporthe oryzae strains that contain the corresponding avirulence gene, AVR-Pita1. Diverse haplotypes of AVR-Pita1 have been identified from isolates of M. oryzae from rice production areas in the United States and worldwide. DNA sequencing and mapping studies have revealed that AVR-Pita1 is highly unstable, while expression analysis and quantitative resistance loci mapping of the Pi-ta locus revealed complex evolutionary mechanisms of Pi-ta-mediated resistance. Among these studies, several Pi-ta transcripts were identified, most of which are probably derived from alternative splicing and exon skipping, which could produce functional resistance proteins that support a new concept of coevolution of Pi-ta and AVR-Pita1. User-friendly DNA markers for Pi-ta have been developed to support marker-assisted selection, and development of new rice varieties with the Pi-ta markers. Genome-wide association studies revealed a link between Pi-ta-mediated resistance and yield components suggesting that rice has evolved a complicated defense mechanism against the blast fungus. In this review, we detail the current understanding of Pi-ta allelic variation, its linkage with rice productivity, AVR-Pita allelic variation, and the coevolution of Pi-ta and AVR-Pita in Oryza species and M. oryzae populations, respectively. We also review the genetic and molecular basis of Pi-ta and AVR-Pita interaction, and its value in marker-assisted selection and engineering resistance.
Nongenetic Inheritance of Induced Resistance in a Wild Annual Plant
Authors: Lankinen Åsa , Abreha Kibrom B. , Alexandersson Erik , Andersson Stefan , Andreasson Erik
Published: April 2016

Nongenetic inheritance (e.g., transgenerational epigenetic effects) has received increasing interest in recent years, particularly in plants. However, most studies have involved a few model species and relatively little is known about wild species in these respects. We investigated transgenerational induced resistance to infection by the devastating oomycete Phytophthora infestans in Solanum physalifolium, a wild relative of cultivated potato. We treated plants with β-aminobutyric acid (BABA), a nontoxic compound acting as an inducing agent, or infected plants with P. infestans. BABA treatment reduced lesion size in detached-leaf assays inoculated by P. infestans in two of three tested genotypes, suggesting that resistance to oomycetes can be induced by BABA within a generation not only in crops or model species but also in wild species directly collected from nature. Both BABA treatment and infection in the parental generation reduced lesions in the subsequent generation in one of two genotypes, indicating a transgenerational influence on resistance that varies among genotypes. We did not detect treatment effects on seed traits, indicating the involvement of a mechanism unrelated to maternal effects. In conclusion, our study provides data on BABA induction and nongenetic inheritance of induced resistance in a wild relative of cultivated potato, implying that this factor might be important in the ecological and agricultural landscape.
Data-driven approaches in the investigation of social perception
Authors: Adolphs Ralph , Nummenmaa Lauri , Todorov Alexander , Haxby James V.
Published: April 2016

The complexity of social perception poses a challenge to traditional approaches to understand its psychological and neurobiological underpinnings. Data-driven methods are particularly well suited to tackling the often high-dimensional nature of stimulus spaces and of neural representations that characterize social perception. Such methods are more exploratory, capitalize on rich and large datasets, and attempt to discover patterns often without strict hypothesis testing. We present four case studies here: behavioural studies on face judgements, two neuroimaging studies of movies, and eyetracking studies in autism. We conclude with suggestions for particular topics that seem ripe for data-driven approaches, as well as caveats and limitations.
From movement kinematics to social cognition: the case of autism
Authors: Cook Jennifer
Published: April 2016

The way in which we move influences our ability to perceive, interpret and predict the actions of others. Thus movements play an important role in social cognition. This review article will appraise the literature concerning movement kinematics and motor control in individuals with autism, and will argue that movement differences between typical and autistic individuals may contribute to bilateral difficulties in reciprocal social cognition.