bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of boron diffusion in MgO in CoFeB∣MgO film stacks using parallel electron energy loss spectroscopy
Authors: Mukherjee Sankha S. , MacMahon David , Bai Feiming , Lee Chih-Ling , Kurinec Santosh K.
Published: February 2009

Boron diffusion in MgO has been investigated in annealed film stacks of sputtered CoFeB∣MgO using transmission electron microscopy and parallel electron energy loss spectroscopy. The analyses show significant B movement when the films are annealed, with the formation of BOx complexes. Characteristic diffusion lengths have been estimated in films annealed at the commonly employed temperature range of 300–400°C for the fabrication of magnetic tunnel junctions. An activation energy of 1.3eV (±0.4eV) has been extracted from these data that represent B diffusion in MgO through vacancies and defect states mediated by the formation of BOx complexes.
Thermal conductivity and interface thermal conductance of amorphous and crystalline Zr47Cu31Al13Ni9 alloys with a Y2O3 coating
Authors: Shukla Nitin C. , Liao Hao-Hsiang , Abiade Jeremiah T. , Liu Fengxiao , Liaw Peter K. , Huxtable Scott T.
Published: February 2009

We examine the thermal conductivity k and interface thermal conductance G for amorphous and crystalline Zr47Cu31Al13Ni9 alloys in contact with polycrystalline Y2O3. Using time-domain thermoreflectance, we find k=4.5 W m−1 K−1 for the amorphous metallic alloy of Zr47Cu31Al13Ni9 and k=5.0 W m−1 K−1 for the crystalline Zr47Cu31Al13Ni9. We also measure G=23 MW m−2 K−1 for the metallic glass/Y2O3 interface and G=26 MW m−2 K−1 for the interface between the crystalline Zr47Cu31Al13Ni9 and Y2O3. The thermal conductivity of the crystalline Y2O3 layer is found to be k=5.0 W m−1 K−1, and the conductances of Al/Y2O3 and Y2O3/Si interfaces are 68 and 45 MW m−2 K−1, respectively.
Threshold voltage control of bottom-contact n-channel organic thin-film transistors using modified drain/source electrodes
Authors: Kitamura Masatoshi , Kuzumoto Yasutaka , Aomori Shigeru , Kamura Masakazu , Na Jong Ho , Arakawa Yasuhiko
Published: February 2009

Bottom-contact n-channel C60 thin-film transistors (TFTs) with drain/source electrodes modified by benzenethiol derivatives have been fabricated to investigate the influence of the modification on the transistor characteristics. Modification using methylbenzenethiol, aminobenzenethiol, and (dimethylamino)benzenethiol having electron-donating groups causes threshold voltages to shift to low voltages. In addition, the modification provides no significant decrease in saturation mobilities. A C60 TFT with (dimethylamino)benzenethiol-modified electrodes has a low threshold voltage of 5.1 V as compared to that of 16.8 V for a TFT with nonmodified electrodes. The threshold-voltage shift is probably because the modification reduces electron-injection barrier height and improves electron injection into organic semiconductors.
Regularization of pattern formation in heteroepitaxial thin films through surface diffusivity modulation
Authors: Kim Y. Y. , Kulkarni S. S. , Krishnaswamy S.
Published: February 2009

A numerical study is presented to demonstrate the influence of local diffusion variation during laser-thermal treatment on the growth dynamics of silicon-germanium thin films. A surface morphology evolution equation is developed with the assumption that the diffusivity is a spatially varying function induced by a sinusoidal surface temperature profile. Results show that an initially flat film evolves into patterns through the thermal modulation, indicating that the growth can be controlled by enhancing local diffusivity. The present study is expected to provide a path for future laser-annealing experiments to produce regularized quantum dots.
Nanoelectrospray aerosols from microporous polymer wick sources
Authors: Tepper Gary , Kessick Royal
Published: February 2009

Nanoelectrospray aerosols were formed from microporous polymer wick sources. Current-voltage characteristics were measured as a function of solution electrical conductivity and surface tension and two distinct electrospray modes were observed. In the first mode, when the maximum capillary flow rate through the wick exceeds the electrospray flow rate, a single electrospray forms from a droplet at the end of the wick. In the second mode, when the maximum capillary flow rate is less than the electrospray flow rate, a multitude of microscopic nanoelectrospray sources are formed from within the surface of the wick tip.
A KTiOPO4 nonlinear photonic crystal for blue second harmonic generation
Authors: Canalias Carlota , Nordlöf Mats , Pasiskevicius Valdas , Laurell Fredrik
Published: February 2009

A nonlinear photonic crystal with a rectangular domain lattice of 6.09×6 μm2 has been fabricated and characterized in flux-grown KTiOPO4. It was used to demonstrate continuous-wave and multiple beam tunable blue second harmonic generation.
Sr
3
Al
2
O
5
Cl
2
:
Ce
3
+
,
Eu
2
+
: A potential tunable yellow-to-white-emitting phosphor for ultraviolet light emitting diodes
Authors: Song Yanhua , Jia Guang , Yang Mei , Huang Yeju , You Hongpeng , Zhang Hongjie
Published: March 2009

The Sr3Al2O5Cl2:Ce3+,Eu2+ phosphors were prepared by solid state reaction. The obtained phosphors exhibit a strong absorption in the UV-visible region and have two intense emission bands at 444 and 609 nm. The energy transfer from the Ce3+ to Eu2+ ions was observed, and the critical distance has been estimated to be about 24.5 Å by spectral overlap method. Furthermore, the developed phosphors can generate lights from yellow-to-white region under the excitation of UV radiation by appropriately tuning the activator content, indicating that they have potential applications as an UV-convertible phosphor for white light emitting diodes.
Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy
Authors: Tackenberg Björn , Jelčić Ilijas , Baerenwaldt Anne , Oertel Wolfgang H. , Sommer Norbert , Nimmerjahn Falk , Lünemann Jan D.
Published: March 2009

The inhibitory Fc-γ receptor FcγRIIB, expressed on myeloid and B cells, has a critical role in the balance of tolerance and autoimmunity, and is required for the antiinflammatory activity of intravenous Ig (IVIG) in various murine disease models. However, the function of FcγRIIB and its regulation by IVIG in human autoimmune diseases are less well understood. Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy, and IVIG is widely used as a first-line initial and maintenance treatment. We found that untreated patients with CIDP, compared with demographically matched healthy controls, showed consistently lower FcγRIIB expression levels on naive B cells, and failed to up-regulate or to maintain up-regulation of FcγRIIB as B cells progressed from the naive to the memory compartment. Concomitantly, the rare −386C/−120A FcγRIIB promoter polymorphism resulting in reduced promoter activity previously associated with autoimmune phenotypes was overrepresented in CIDP. Also, FcγRIIB protein expression was up-regulated on monocytes and B cells after clinically effective IVIG therapy. Thus, our results suggest that the inhibitory FcγRIIB is impaired at a critical B cell differentiation checkpoint in CIDP, and that modulating FcγRIIB expression might be a promising approach to efficiently limit antibody-mediated immunopathology in CIDP.
Distinct modes of gene regulation by a cell-specific transcriptional activator
Authors: Sengupta Tanushri , Cohet Nathalie , Morlé François , Bieker James J.
Published: February 2009

The architectural layout of a eukaryotic RNA polymerase II core promoter plays a role in general transcriptional activation. However, its role in tissue-specific expression is not known. For example, differing modes of its recognition by general transcription machinery can provide an additional layer of control within which a single tissue-restricted transcription factor may operate. Erythroid Kruppel-like factor (EKLF) is a hematopoietic-specific transcription factor that is critical for the activation of subset of erythroid genes. We find that EKLF interacts with TATA binding protein-associated factor 9 (TAF9), which leads to important consequences for expression of adult β-globin. First, TAF9 functionally supports EKLF activity by enhancing its ability to activate the β-globin gene. Second, TAF9 interacts with a conserved β-globin downstream promoter element, and ablation of this interaction by β-thalassemia-causing mutations decreases its promoter activity and disables superactivation. Third, depletion of EKLF prevents recruitment of TAF9 to the β-globin promoter, whereas depletion of TAF9 drastically impairs β-promoter activity. However, a TAF9-independent mode of EKLF transcriptional activation is exhibited by the α-hemoglobin-stabilizing protein (
AHSP
) gene, which does not contain a discernable downstream promoter element. In this case, TAF9 does not enhance EKLF activity and depletion of TAF9 has no effect on
AHSP
promoter activation. These studies demonstrate that EKLF directs different modes of tissue-specific transcriptional activation depending on the architecture of its target core promoter.
Disproportionation and self-sorting in molecular encapsulation
Authors: Ajami Dariush , Hou Jun-Li , Dale Trevor J. , Barrett Elizabeth , Rebek Julius
Published: February 2009

Self-assembled capsules are nanoscale structures made up of multiple synthetic subunits held together by weak intermolecular forces. They act as host structures that can completely surround small molecule guests of the appropriate size, shape and chemical surface. Like their biological counterparts, multimeric enzymes and receptors, the subunits of the capsules are generally identical, and lead to homomeric assemblies of high symmetry. In both biological and synthetic systems small variations in structures are tolerated and lead to heteromeric assemblies with slightly different recognition properties. The synthetic capsules are dynamic, with lifetimes from milliseconds to hours, and allow the direct spectroscopic observation of smaller molecules inside, under ambient conditions at equilibrium in solution. We report here the assembly of hybrid capsules made up of 2 very different structures, both capable of forming their own homomeric capsules through hydrogen bonding. These hybrids exhibit host properties that differ markedly from the parent capsules, and suggest that other capsules may emerge from seemingly unrelated modules that have curved surfaces and are rich in hydrogen bonding capabilities.
Noonan syndrome cardiac defects are caused by
PTPN11
acting in endocardium to enhance endocardial-mesenchymal transformation
Authors: Araki Toshiyuki , Chan Gordon , Newbigging Susan , Morikawa Lily , Bronson Roderick T. , Neel Benjamin G.
Published: February 2009

Noonan syndrome (NS), the most common single-gene cause of congenital heart disease, is an autosomal dominant disorder that also features proportionate short stature, facial abnormalities, and an increased risk of myeloproliferative disease. Germline-activating mutations in
PTPN11
, which encodes the protein tyrosine phosphatase SHP2, cause about half of NS cases; other causative alleles include
KRAS
,
SOS1
, and
RAF1
mutants. We showed previously that knock-in mice bearing the NS mutant

Ptpn11
D61G

on a mixed 129S4/SvJae X C57BL6/J background exhibit all major NS features, including a variety of cardiac defects, with variable penetrance. However, the cellular and molecular mechanisms underlying NS cardiac defects and whether genetic background and/or the specific NS mutation contribute to the NS phenotype remained unclear. Here, using an inducible knock-in approach, we show that all cardiac defects in NS result from mutant Shp2 expression in the endocardium, not in the myocardium or neural crest. Furthermore, the penetrance of NS defects is affected by genetic background and the specific
Ptpn11
allele. Finally, ex vivo assays and pharmacological approaches show that NS mutants cause cardiac valve defects by increasing Erk MAPK activation, probably downstream of ErbB family receptor tyrosine kinases, extending the interval during which cardiac endocardial cells undergo endocardial-mesenchymal transformation. Our data provide a mechanistic underpinning for the cardiac defects in this disorder.
Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of
Escherichia coli
proteins
Authors: Niwa Tatsuya , Ying Bei-Wen , Saito Katsuyo , Jin WenZhen , Takada Shoji , Ueda Takuya , Taguchi Hideki
Published: February 2009

Protein folding often competes with intermolecular aggregation, which in most cases irreversibly impairs protein function, as exemplified by the formation of inclusion bodies. Although it has been empirically determined that some proteins tend to aggregate, the relationship between the protein aggregation propensities and the primary sequences remains poorly understood. Here, we individually synthesized the entire ensemble of
Escherichia coli
proteins by using an in vitro reconstituted translation system and analyzed the aggregation propensities. Because the reconstituted translation system is chaperone-free, we could evaluate the inherent aggregation propensities of thousands of proteins in a translation-coupled manner. A histogram of the solubilities, based on data from 3,173 translated proteins, revealed a clear bimodal distribution, indicating that the aggregation propensities are not evenly distributed across a continuum. Instead, the proteins can be categorized into 2 groups, soluble and aggregation-prone proteins. The aggregation propensity is most prominently correlated with the structural classification of proteins, implying that the prediction of aggregation propensity requires structural information about the protein.
A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol
Authors: Tong Jiansong , Borbat Peter P. , Freed Jack H. , Shin Yeon-Kyun
Published: February 2009

Neurotransmitter release at the synapse requires membrane fusion. The SNARE complex, composed of the plasma membrane t-SNAREs syntaxin 1A and SNAP-25 and the vesicle v-SNARE synaptobrevin, mediates the fusion of 2 membranes. Synaptic vesicles contain unusually high cholesterol, but the exact role of cholesterol in fusion is not known. In this study, cholesterol was found to stimulate SNARE-mediated lipid mixing of proteoliposomes by a factor of 5 at a physiological concentration. Surprisingly, however, the stimulatory effect was more pronounced when cholesterol was on the v-SNARE side than when it was on the t-SNARE side. Site-directed spin labeling and both continuous wave (CW) and pulsed EPR revealed that cholesterol induces a conformational change of the v-SNARE transmembrane domain (TMD) from an open scissors-like dimer to a parallel dimer. When the TMD was forced to form a parallel dimer by the disulfide bond, the rate was stimulated 2.3-fold even without cholesterol, supporting the relevance of the open-to-closed conformational change to the fusion activity. The open scissors-like conformation may be unfavorable for fusion and cholesterol may relieve this inhibitory factor.
Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin
Authors: Leiman Petr G. , Basler Marek , Ramagopal Udupi A. , Bonanno Jeffrey B. , Sauder J. Michael , Pukatzki Stefan , Burley Stephen K. , Almo Steven C. , Mekalanos John J.
Published: February 2009

Protein secretion is a common property of pathogenic microbes. Gram-negative bacterial pathogens use at least 6 distinct extracellular protein secretion systems to export proteins through their multilayered cell envelope and in some cases into host cells. Among the most widespread is the newly recognized Type VI secretion system (T6SS) which is composed of 15–20 proteins whose biochemical functions are not well understood. Using crystallographic, biochemical, and bioinformatic analyses, we identified 3 T6SS components, which are homologous to bacteriophage tail proteins. These include the tail tube protein; the membrane-penetrating needle, situated at the distal end of the tube; and another protein associated with the needle and tube. We propose that T6SS is a multicomponent structure whose extracellular part resembles both structurally and functionally a bacteriophage tail, an efficient machine that translocates proteins and DNA across lipid membranes into cells.
Dicing of viral replication intermediates during silencing of latent
Drosophila
viruses
Authors: Flynt Alex , Liu Na , Martin Raquel , Lai Eric C.
Published: February 2009

Previous studies revealed roles for RNA interference (RNAi) in the immediate cellular response to viral infection in plants, nematodes and flies. However, little is known about how RNAi combats viruses during persistent or latent infections. Our analysis of small RNAs cloned from
Drosophila
cells latently infected with Flock House Virus (FHV) failed to reveal signatures of bulk degradation of the viral genome. Instead, this + strand virus specifically generated Dicer-2-dependent, 21-nucleotide siRNAs that derived in equal proportion from + and − strands. Curiously, luciferase reporters that are fully complementary to abundant viral siRNAs were poorly repressed. Moreover, although the viral siRNAs that were incorporated into an effector complex associated with Argonaute2, bulk FHV siRNAs in latently infected cells were not loaded into any Argonaute protein. Together, these data suggest that direct dicing of viral replication intermediates plays an important role in maintaining the latent viral state. In addition, the denial of bulk viral siRNAs from effector complexes suggests that criteria beyond the structural competency of RNA duplexes influence the assembly of functional silencing complexes.
The phage λ major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system
Authors: Pell Lisa G. , Kanelis Voula , Donaldson Logan W. , Lynne Howell P. , Davidson Alan R.
Published: February 2009

Most bacteriophages possess long tails, which serve as the conduit for genome delivery. We report the solution structure of the N-terminal domain of gpV, the protein comprising the major portion of the noncontractile phage λ tail tube. This structure is very similar to a previously solved tail tube protein from a contractile-tailed phage, providing the first direct evidence of an evolutionary connection between these 2 distinct types of phage tails. A remarkable structural similarity is also seen to Hcp1, a component of the bacterial type VI secretion system. The hexameric structure of Hcp1 and its ability to form long tubes are strikingly reminiscent of gpV when it is polymerized into a tail tube. These data coupled with other similarities between phage and type VI secretion proteins support an evolutionary relationship between these systems. Using Hcp1 as a model, we propose a polymerization mechanism for gpV involving several disorder-to-order transitions.
Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine
Authors: Fre Silvia , Pallavi S. K. , Huyghe Mathilde , Laé Marick , Janssen Klaus-Peter , Robine Sylvie , Artavanis-Tsakonas Spyros , Louvard Daniel
Published: February 2009

Notch and Wnt signals play essential roles in intestinal development and homeostasis, yet how they integrate their action to affect intestinal morphogenesis is not understood. We examined the interplay between these two signaling pathways in vivo, by modulating Notch activity in mice carrying either a loss- or a gain-of-function mutation of Wnt signaling. We find that the dramatic proliferative effect that Notch signals have on early intestinal precursors requires normal Wnt signaling, whereas its influence on intestinal differentiation appears independent of Wnt. Analogous experiments in
Drosophila
demonstrate that the synergistic effects of Notch and Wnt are valid across species. We also demonstrate a striking synergy between Notch and Wnt signals that results in inducing the formation of intestinal adenomas, particularly in the colon, a region rarely affected in available mouse tumor models, but the primary target organ in human patients. These studies thus reveal a previously unknown oncogenic potential of Notch signaling in colorectal tumorigenesis that, significantly, is supported by the analysis of human tumors. Importantly, our experimental evidence raises the possibility that Notch activation might be an essential initial event triggering colorectal cancer.
Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12
Authors: Inui Masanori , Kikuchi Yuki , Aoki Naoko , Endo Shota , Maeda Tsutomu , Sugahara-Tobinai Akiko , Fujimura Shion , Nakamura Akira , Kumanogoh Atsushi , Colonna Marco , Takai Toshiyuki
Published: February 2009

Osteoclasts, cells of myeloid lineage, play a unique role in bone resorption, maintaining skeletal homeostasis in concert with bone-producing osteoblasts. Osteoclast development and maturation (osteoclastogenesis) is driven by receptor activator of NF-κB ligand and macrophage-colony stimulating factor and invariably requires a signal initiated by immunoreceptor tyrosine-based activation motif (ITAM)-harboring Fc receptor common γ chain or DNAX-activating protein (DAP)12 (also referred to as KARAP or TYROBP) that associates with the cognate immunoreceptors. Here, we show that a third adaptor, YINM costimulatory motif-harboring DAP10, triggers osteoclastogenesis and bone remodeling. DAP10-deficient (DAP10−/−) mice become osteopetrotic with age, concomitant with a reduction in osteoclasts. The DAP10-associating receptor was identified as myeloid DAP12-associating lectin-1 (MDL-1), whose physiologic function has not been found. MDL-1-mediated stimulation of osteoclast precursor cells resulted in augmented osteoclastogenesis in vitro. MDL-1 associates with both DAP12 and DAP10 in osteoclasts and bone marrow-derived macrophages, where DAP10 association depends almost entirely on DAP12, suggesting a formation of MDL-1–DAP12/DAP10 trimolecular complexes harboring ITAM/YINM stimulatory/costimulatory motifs within a complex that could be a novel therapeutic target for skeletal and inflammatory diseases.
MerTK regulates thymic selection of autoreactive T cells
Authors: Wallet Mark A. , Flores Rafael R. , Wang Yaming , Yi Zuoan , Kroger Charles J. , Mathews Clayton E. , Earp H. Shelton , Matsushima Glenn , Wang Bo , Tisch Roland
Published: February 2009

T cell-mediated autoimmune diseases such as type 1 diabetes (T1D) are believed to be the result in part of inefficient negative selection of self-specific thymocytes. However, the events regulating thymic negative selection are not fully understood. In the current study, we demonstrate that nonobese diabetic (NOD) mice lacking expression of the Mer tyrosine kinase (MerTK) have reduced inflammation of the pancreatic islets and fail to develop diabetes. Furthermore, NOD mice deficient in MerTK expression (Mer−/−) exhibit a reduced frequency of β cell-specific T cells independent of immunoregulatory effectors. The establishment of bone marrow chimeric mice demonstrated that the block in β cell autoimmunity required hematopoietic-derived cells lacking MerTK expression. Notably, fetal thymic organ cultures and self-peptide administration showed increased thymic negative selection in Mer−/−mice. Finally, thymic dendritic cells (DC) prepared from Mer−/−mice exhibited an increased capacity to induce thymocyte apoptosis in a peptide-specific manner in vitro. These findings provide evidence for a unique mechanism involving MerTK-mediated regulation of thymocyte negative selection and thymic DC, and suggest a role for MerTK in contributing to β cell autoimmunity.
V600E
BRAF is associated with disabled feedback inhibition of RAF–MEK signaling and elevated transcriptional output of the pathway
Authors: Pratilas Christine A. , Taylor Barry S. , Ye Qing , Viale Agnes , Sander Chris , Solit David B. , Rosen Neal
Published: February 2009

Tumors with mutant BRAF and those with receptor tyrosine kinase (RTK) activation have similar levels of phosphorylated ERK, but only the former depend on ERK signaling for proliferation. The mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK)/ERK-dependent transcriptional output was defined as the genes whose expression changes significantly 8 h after MEK inhibition. In
V600E
BRAF cells, this output is comprised of 52 genes, including transcription factors that regulate transformation and members of the dual specificity phosphatase and Sprouty gene families, feedback inhibitors of ERK signaling. No such genes were identified in RTK tumor cells, suggesting that ERK pathway signaling output is selectively activated in BRAF mutant tumors. We find that RAF signaling is feedback down-regulated in RTK cells, but is insensitive to this feedback in BRAF mutant tumors. Physiologic feedback inhibition of RAF/MEK signaling down-regulates ERK output in RTK cells; evasion of this feedback in mutant BRAF cells is associated with increased transcriptional output and MEK/ERK-dependent transformation.
Self-consistent simulation of torque generation by radial current due to fast particles
Authors: Honda M. , Takizuka T. , Fukuyama A. , Yoshida M. , Ozeki T.
Published: February 2009

The generation of toroidal rotation due to the radial current torque induced by the charge separation is studied by using the one-dimensional multi-fluid transport code TASK/TX. Owing to the effect of the drift motion, the charge separation occurs as long as fast neutrals, typically from near-perpendicular NBI, are ionized. Coupling the TASK/TX code with the orbit-following Monte Carlo code (OFMC), we have shown that the toroidal rotation is driven due to the generation of the radial current j
bulk flowing in the bulk plasma with the near-perpendicular NBI. The simulations have clarified that the NB on the equatorial plane drives the toroidal rotation most efficiently from the aspects of the collisional and j
bulk × B torques. The j
bulk × B torque becomes a major driver of the rotation in a high density plasma, replacing the collisional torque. In a steady state, the toroidal rotation driven by the j
bulk × B torque is determined by the balance among the torque, the viscosity, the convection, the friction with neutrals and the loss of momentum due to charge exchange.
GeNGe: systematic generation of gene regulatory networks
Authors: Hache Hendrik , Wierling Christoph , Lehrach Hans , Herwig Ralf
Published: February 2009

Summary: The analysis of gene regulatory networks (GRNs) is a central goal of bioinformatics highly accelerated by the advent of new experimental techniques, such as RNA interference. A battery of reverse engineering methods has been developed in recent years to reconstruct the underlying GRNs from these and other experimental data. However, the performance of the individual methods is poorly understood and validation of algorithmic performances is still missing to a large extent. To enable such systematic validation, we have developed the web application GeNGe (GEne Network GEnerator), a controlled framework for the automatic generation of GRNs. The theoretical model for a GRN is a non-linear differential equation system. Networks can be user-defined or constructed in a modular way with the option to introduce global and local network perturbations. Resulting data can be used, e.g. as benchmark data for evaluating GRN reconstruction methods or for predicting effects of perturbations as theoretical counterparts of biological experiments.

Availability: Available online at http://genge.molgen.mpg.de

Contact:  hache@molgen.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Textual data compression in computational biology: a synopsis
Authors: Giancarlo Raffaele , Scaturro Davide , Utro Filippo
Published: February 2009

Motivation: Textual data compression, and the associated techniques coming from information theory, are often perceived as being of interest for data communication and storage. However, they are also deeply related to classification and data mining and analysis. In recent years, a substantial effort has been made for the application of textual data compression techniques to various computational biology tasks, ranging from storage and indexing of large datasets to comparison and reverse engineering of biological networks.

Results: The main focus of this review is on a systematic presentation of the key areas of bioinformatics and computational biology where compression has been used. When possible, a unifying organization of the main ideas and techniques is also provided.

Availability: It goes without saying that most of the research results reviewed here offer software prototypes to the bioinformatics community. The Supplementary Material provides pointers to software and benchmark datasets for a range of applications of broad interest. In addition to provide reference to software, the Supplementary Material also gives a brief presentation of some fundamental results and techniques related to this paper. It is at: http://www.math.unipa.it/∼raffaele/suppMaterial/compReview/

Contact:  raffaele@math.unipa.it
Understanding the ‘epidemic of heart failure’: a systematic review of trends in determinants of heart failure
Authors: Najafi Farid , Jamrozik Konrad , Dobson Annette J.
Published: February 2009

Aims

We conducted a systematic review of recent studies investigating trends in the epidemiology of heart failure (HF).

Methods and results

We fitted simple linear regression models of rates against calendar year for mortality and hospital admission. Based on Population Attributable Fractions (PAFs) from the NHANES I Epidemiological Follow‐up Study and self‐reported prevalences of risk factors for HF, the estimated changes in numbers of new cases of HF in Australia were calculated from 1995 to 2005. A clear decline in mortality from HF and some data on decreases in admissions to hospitals for HF, as well as the lack of reports showing an increase in the incidence of HF, all argue against the existence of an ‘epidemic’ of HF. However, most reports on trends in HF survival have shown a secular improvement. The latter, together with population aging, are major factors that may increase the caseload of HF. Against this background of conflicting influences, we estimate that in Australia, the inflow into the caseload of HF decreased by 1.6% among people aged ≥55 years in 2005 relative to 1995.

Conclusion

Available evidence does not support an increase in the caseload of HF over recent years. Taking all of the influences on the epidemiology of HF together, it is likely that the number of new cases of HF will rise over the next few years, even if the incidence rate falls, chiefly because the elderly population is expanding so quickly.
Dexmedetomidine Reduces Long-term Potentiation in Mouse Hippocampus
Authors: Takamatsu Isao , Iwase Ayano , Ozaki Makoto , Kazama Tomiei , Wada Keiji , Sekiguchi Masayuki
Published: March 2009

Background

Dexmedetomidine (Precedex; Abbott Laboratories, Abbott Park, IL) is a selective alpha2-adrenergic agonist that also has affinity for imidazoline receptors. In clinical studies, dexmedetomidine has sedative effects and impairs memory, but the action of dexmedetomidine on synaptic plasticity in the brain has yet to be established. In the present study, the authors investigated the effects of dexmedetomidine on two forms of synaptic plasticity-long-term potentiation (LTP) and paired-pulse facilitation-in the CA1 region of mouse hippocampal slices.

Methods

The authors recorded Schaffer collateral-evoked field excitatory postsynaptic potentials from mouse hippocampal slices in CA1 stratum radiatum. The slope of the rising phase of the field excitatory postsynaptic potential was used to estimate the strength of synaptic transmission.

Results

Application of dexmedetomidine for 20 min before "theta burst" stimulation dose-dependently attenuated LTP, and half-inhibitory concentration of dexmedetomidine was 28.6 +/- 5.7 nm. The inhibitory effect of dexmedetomidine on LTP was not abolished by an alpha2-adrenoceptor antagonist (yohimbine), an imidazoline type 1 receptor and alpha2-adrenoceptor antagonist (efaroxan), an alpha1-adrenoceptor antagonist (prazosin), or a gamma-aminobutyric acid type A receptor antagonist (picrotoxin). However, an imidazoline type 2 receptor and alpha2-adrenoceptor antagonist (idazoxan) completely blocked the dexmedetomidine-induced attenuation. Furthermore, 2-benzofuranyl-2-imidaloline, a selective imidazoline type 2 receptor ligand, reduced LTP. 2-(4,5-dihydroimidaz-2-yl)-quinoline, another imidazoline type 2 receptor ligand, abolished the 2-benzofuranyl-2-imidaloline-induced attenuation, but the inhibitory effect of dexmedetomidine on LTP was not abolished by 2-(4,5-dihydroimidaz-2-yl)-quinoline. Dexmedetomidine did not affect paired-pulse facilitation.

Conclusion

Dexmedetomidine impairs LTP in area CA1 of the mouse hippocampus via imidazoline type 2 receptors and alpha2-adrenoceptors.
Long‐term Adverse Outcomes of Low Birth Weight, Increased Somatic Growth Rates, and Alterations of Body Composition in the Premature Infant: Review of the Evidence
Authors: Greer Frank R
Published: March 2009

In appropriate‐for‐gestational‐age preterm infants, data are reviewed to support that both high and low nutrient intakes, as well as fast or slow rates of growth in the neonatal intensive care unit, have long‐term adverse (or even positive) effects on body weight and the metabolic syndrome later in life. Though more studies are needed, it is concluded that it is likely that any such effects will be relatively small compared with other risk factors such as parental weight and various lifestyle factors. At the present time, there is little evidence that negates the goal of maximizing nutritional support for the very low birth weight infant in the neonatal period.
Nutrient Supplies for Optimal Health in Preterm Infants
Authors: Hay William W
Published: March 2009

The most commonly recommended standard for postnatal nutrition of very preterm infants is one that meets the unique nutritional requirements of the growing human fetus and duplicates normal in utero human fetal growth (weight and body composition) and development. Normal fetal nutrition, therefore, may be a useful guide for designing postnatal nutritional strategies in very preterm infants who need to grow and develop outside the uterus. Such information indicates that normal fetal nutrition requires certain nutrients in optimal amounts and certain growth‐promoting hormones in response to nutrient supply that together support optimal fetal growth and development; these include oxygen, glucose, lipids, amino acids, and insulin. Interestingly, nutrient restriction and nutrient excess in the fetus, while leading to different phenotypes, produce a similar phenotype in later life characterized as the “metabolic syndrome,” consisting of obesity, insulin resistance, diabetes, and cardiovascular disease. After birth, preterm infants—who almost universally are not fed as much as normally growing fetuses receive in nutrient supply via the placenta—also end up with a higher incidence of short stature and a predisposition to the metabolic syndrome, whereas those fed excessive amounts of energy and who develop excessive growth primarily of adipose tissue in early life (rapid, positive crossing of weight‐for‐length centiles) also develop a higher incidence of the metabolic syndrome. It is clear, therefore, that just the right amount of the essential nutrients is required to produce optimal outcome; this is as true for the preterm infant as it is for the fetus.
Mother's Own Milk, Donor Human Milk, and Preterm Formulas in the Feeding of Extremely Premature Infants
Authors: Schanler Richard J
Published: March 2009

Significant benefits to infant host defense, sensory‐neural development, gastrointestinal maturation, and some aspects of nutritional status are observed when premature infants are fed their mothers' own milk. A reduction in infection‐related morbidity in human milk‐fed premature infants has been reported in nearly 1 dozen descriptive, and a few quasirandomized, studies in the past 25 years. Studies on neurodevelopmental outcomes have reported significantly positive effects for human milk intake on mental and motor development, intelligence quotient, and visual acuity compared with the feeding of formula. Human milk‐fed infants also have decreased rates of rehospitalization after discharge. It is unclear how much human milk is needed to provide protection or at what postnatal age the protective effects maximize. The data suggest that a specific dose of milk may be needed to confer protection. A detailed composition analysis of milk obtained from women delivering before 30 weeks of gestation is needed to determine if the “immature” milk contains the same functional bioactive factors as more mature milk. Furthermore, lactation strategies should be sought that increase mother's own milk production.
Weaning Preterm Infants: An Open Issue
Authors: Fanaro Silvia , Vigi Vittorio
Published: March 2009

Survival rates for very low birth weight (VLBW) and extremely low birth weight infants have substantially increased during the past few decades. Most of these infants pose new and difficult problems related in particular to neurodevelopmental outcome and growth impairment. In fact, a high percentage of very low birth weight infants fail to achieve their growth potential and experience postnatal growth restriction. Because of this in‐hospital growth failure and nutrient deficits, correct nutritional intervention after hospital discharge must be instituted to avoid postnatal malnutrition and to correct the acquired deficit. Nutrient‐enriched formulas for several months after discharge have shown some benefits, although their clinical value remains unclear. Weaning, which certainly represents a relevant source of nutrients for the preterm infant, has attracted little attention until now. There are no precise guidelines on this topic, and too often weaning practices are left totally to the parents, without considering the specific nutritional needs of the single infant.
Effect of Treatment of Hepatic Histopathology in Children and Adolescents With Autoimmune Hepatitis
Authors: Ferreira Alexandre Rodrigues , Roquete Mariza Leitão Valadares , Toppa Nivaldo H , de Castro Lúcia Porto Fonseca , Fagundes Eleonora Druve Tavares , Penna Francisco José
Published: March 2009

Objective:

To evaluate the effects of treatment on liver histopathology of children and adolescents diagnosed with autoimmune hepatitis.

Patients and Methods:

Histopathological evaluation of liver biopsies performed at diagnosis or early during treatment, compared with biopsies after immunosuppressive treatment of 20 children and adolescents diagnosed with autoimmune hepatitis who presented clinical and biochemical remission for at least 24 months. Liver histopathology was assessed by 2 pathologists. Agreement between their interpretations was analyzed with κ statistics.

Results:

The age at diagnosis of the 20 patients varied from 1.7 years to 11.6 years (median = 6.6 years); 18 were females. The mean duration of clinical and biochemical remission, up to performance of liver biopsy, was 4.1 years. The mean interval between the initial and posttreatment biopsies was 4.6 years (range 2–9.7 years). Assessing the necroinflammatory activity, a mean reduction by 6.3 (observer 1) and 7.3 (observer 2) in the grading score was observed (P = 0.00000). When staging was assessed, a mean reduction by 1.8 (observers 1 and 2) in the score was observed after treatment (P = 0.00008), and there was no progression toward cirrhosis. No regression of cirrhosis was observed.

Conclusions:

On histopathological evaluation, the immunosuppressive treatment improved the fibrosis scores, with an arrest in its progression and no development into cirrhosis. Fibrosis control is mainly associated with regression of necroinflammatory activity, which is the main treatment component in autoimmune hepatitis.
Very Low Birth Weight Infants as a Model to Study Genetic Influences on Neonatal Weight Gain
Authors: Spiegler Juliane , Kattner Evelyn , Vochem Matthias , Küster Helmuth , Möller Jens , Müller Dirk , Kribs Angela , Segerer Hugo , Wieg Christian , Nikischin Werner , Wense Axel von der , Gebauer Corinna , Herting Egbert , Göpel Wolfgang
Published: March 2009

In a cohort of 829 preterm infants (birth weight below 1500 g) we identified 13 monozygotic, 10 same‐sex dizygotic, and 12 same‐sex matched singleton pairs. The difference in daily weight gain within pairs was significantly lower in monozygotic twins compared with dizygotic twins or matched singleton pairs. Our data support a strong genetic influence on postnatal growth in preterm infants. Therefore, weight gain of preterm infants may be an interesting model to study polymorphic variants of genes regulating neonatal resorption, metabolism, or energy expenditure, and their influence on weight gain in preterm infants.
Back to the Basic Sciences: An Innovative Approach to Teaching Senior Medical Students How Best to Integrate Basic Science and Clinical Medicine
Authors: Spencer Abby L. , Brosenitsch Teresa , Levine Arthur S. , Kanter Steven L.
Published: March 2009

Abraham Flexner persuaded the medical establishment of his time that teaching the sciences, from basic to clinical, should be a critical component of the medical student curriculum, thus giving rise to the “preclinical curriculum.” However, students’ retention of basic science material after the preclinical years is generally poor. The authors believe that revisiting the basic sciences in the fourth year can enhance understanding of clinical medicine and further students’ understanding of how the two fields integrate. With this in mind, a return to the basic sciences during the fourth year of medical school may be highly beneficial. The purpose of this article is to (1) discuss efforts to integrate basic science into the clinical years of medical student education throughout the United States and Canada, and (2) describe the highly developed fourth-year basic science integration program at the University of Pittsburgh School of Medicine. In their critical review of medical school curricula of 126 U.S. and 17 Canadian medical schools, the authors found that only 19% of U.S. medical schools and 24% of Canadian medical schools require basic science courses or experiences during the clinical years, a minor increase compared with 1985. Curricular methods ranged from simple lectures to integrated case studies with hands-on laboratory experience. The authors hope to advance the national discussion about the need to more fully integrate basic science teaching throughout all four years of the medical student curriculum by placing a curricular innovation in the context of similar efforts by other U.S. and Canadian medical schools.
Management of Tracheobronchial Stenoses With Endoprostheses: Experience With 103 Patients and 11 Models
Authors: Merrot Olivier , Buiret Guillaume , Gleizal Arnaud , Poupart Marc , Pignat Jean‐Christian
Published: March 2009

Objective: To describe in a retrospective study our experience in endoscopic management of tracheobronchial stenosis with 145 stents (11 different models).

Methods: We analyzed the medical records of 103 patients (67 males and 36 females) who underwent the placement of prosthesis for any causes of tracheobronchial stenoses between 1990 and 2005.

Results: A total of 145 prostheses were placed. Of these, 96.1% of the patients had a relief of dyspnea, and 73.8% had only one prosthesis. Stent removal and replacement were significantly linked with etiologies (more frequently in patients with an inflammatory component), but not with the type of stent.

Conclusion: Endostenting is a safe and effective treatment for tracheobronchial stenoses. Removal and replacements were due to etiologies of the strictures, but not to the type of stent. Stenoses with an inflammatory component were prone to iterative stenting. Only benign diseases that are a contra‐indication to open surgery should be treated by endoscopic stenting.
Evaluation of a Novel Stool Native Catalase Antigen Test for Helicobacter pylori Infection in Asymptomatic North American Children
Authors: Cardenas Victor M , Dominguez Delfina C , Puentes Flor A , Aragaki Corinne C , Goodman Karen J , Graham David Y , Fukuda Yoshihiro
Published: March 2009

Rapid immunochromatographic tests for Helicobacter pylori infection have been developed to allow “near‐patient” testing. We therefore performed a pilot study to test a rapid immunochromatographic stool antigen test for the diagnosis of H pylori infection in asymptomatic children. We tested stool specimens collected from children participating in a cohort study in the United States and Mexico. H pylori–positive status was defined by positivity on at least 2 tests: a commercial H pylori stool antigen enzyme immunoassay, an immunoglobulin G antibody enzyme immunoassay, and the 13C‐urea breath test. Negative H pylori status was defined by negative findings of all of these tests. Of 52 children (22 girls, 30 boys) 25 were H pylori–positive, 19 H pylori–negative, and 8 uncertain (eg, presumably negative; positive findings on 1 of the 3 noninvasive tests). The sensitivity and specificity of the new stool antigen test for those with definite H pylori status were 100% (exact 95% CI 86.3%–100% and 82.4%–100%, respectively). This rapid stool antigen test may prove useful for point‐of‐care testing and epidemiological field studies. Larger prospective studies are needed in symptomatic and asymptomatic children for more precise estimates.
Looking for a Relation Between Serum Leptin Concentration and Body Composition Parameters in Healthy Term Infants in the First 6 Months of Life
Authors: Savino Francesco , Liguori Stefania Alfonsina , Fissore Maria Francesca , Palumeri Elisabetta , Calabrese Roberto , Oggero Roberto , Silvestro Leandra , Miniero Roberto
Published: March 2009

We carried out a cross‐sectional study of 115 healthy infants, younger than 6 months old, exclusively breast‐fed or formula‐fed, to investigate correlations between circulating leptin concentrations and body composition measurements. Serum leptin was evaluated with radioimmunoassay, and body composition with bioelectrical impedance analysis. Multiple regression analysis showed a relationship between serum leptin and body mass index in the entire study population (P = 0.042). There was a significant negative relationship between serum leptin and phase angle (P = 0.006) in formula‐fed infants. Serum leptin was positively related to subscapular skinfold thickness (P = 0.055) and negatively to reactance (P = 0.057) only in formula‐fed infants, although the differences were just below significance. Serum leptin concentration was higher in breast‐fed infants (P = 0.002), and was not correlated with body composition parameters. This study indicates that there is a relation between leptin and infant body composition in the first months of life, although the link needs to be explored further.