bluuebunny/crossref_metadata_2025_split huggingface dataset:
A putative twin-arginine translocation system in the phytopathogenic bacterium Xylella fastidiosa
Authors: Ciapina Luciane Prioli , Picchi Simone Cristina , Lacroix Jean-Marie , de Macedo Lemos Eliana Gertrudes , Ödberg-Ferragut Carmen 
Published: February 2011

The twin-arginine translocation (Tat) pathway of the xylem-limited phytopathogenic bacterium Xylella fastidiosa strain 9a5c, responsible for citrus variegated chlorosis, was explored. The presence of tatA, tatB, and tatC in the X. fastidiosa genome together with a list of proteins harboring 2 consecutive arginines in their signal peptides suggested the presence of a Tat pathway. The functional Tat dependence of X. fastidiosa OpgD was examined. Native or mutated signal peptides were fused to the β-lactamase. Expression of fusion with intact signal peptides mediated high resistance to ampicillin in Escherichia coli tat+but not in the E. coli tat null mutant. The replacement of the 2 arginines by 2 lysines prevented the export of β-lactamase in E. coli tat+, demonstrating that X. fastidiosa OpgD carries a signal peptide capable of engaging the E. coli Tat machinery. RT–PCR analysis revealed that the tat genes are transcribed as a single operon. tatA, tatB, and tatC genes were cloned. Complementation assays in E. coli devoid of all Tat or TatC components were unsuccessful, whereas X. fastidiosa Tat components led to a functional Tat translocase in E. coli TatB-deficient strain. Additional experiments implicated that X. fastidiosa TatB component could form a functional heterologous complex with the E. coli TatC component.
Temporal and spatial interactions between an obligate predator, the Eurasian lynx (Lynx lynx), and a facultative scavenger, the wolverine (Gulo gulo)
Authors: Mattisson Jenny , Persson Jens , Andrén Henrik , Segerström Peter 
Published: February 2011

Interspecific interactions between sympatric carnivores can be important for the behaviour and demography of involved species. We studied spatial and temporal interactions between an obligate predator, the Eurasian lynx ( Lynx lynx (L., 1758)), and a facultative scavenger, the wolverine ( Gulo gulo (L., 1758)). Wolverines are known to utilize lynx-killed reindeer ( Rangifer tarandus tarandus (L., 1758)) and may benefit from being sympatric with lynx if interference competition is low. We used individual location data from 9 lynx and 17 wolverines to analyse interaction between inter- and intra-specific dyads (n = 195). We found no spatial segregation between lynx and wolverines and we observed no attraction or avoidance between individuals of the two species, independent of proportion of home-range overlap. This opposed our prediction that wolverines will show direct or delayed attraction to lynx. Wolverines may still benefit by scavenging lynx-killed reindeer while avoiding direct encounters with the lynx. Within species, we found attraction between males and females, increasing with proportion of overlap for lynx. Attraction was also found between consexual lynx, while consexual wolverines showed little home-range overlap (7%–9%) and neutral temporal interaction, indicating territoriality. Individual space use may be more influenced by conspecific interactions than by other species.
Lightweight modular staging
Authors: Rompf Tiark , Odersky Martin 
Published: February 2011

Software engineering demands generality and abstraction, performance demands specialization and concretization. Generative programming can provide both, but the effort required to develop high-quality program generators likely offsets their benefits, even if a multi-stage programming language is used.
We present lightweight modular staging, a library-based multi-stage programming approach that breaks with the tradition of syntactic quasi-quotation and instead uses only types to distinguish between binding times. Through extensive use of component technology, lightweight modular staging makes an optimizing compiler framework available at the library level, allowing programmers to tightly integrate domain-specific abstractions and optimizations into the generation process.
We argue that lightweight modular staging enables a form of language virtualization, i.e. allows to go from a pure-library embedded language to one that is practically equivalent to a stand-alone implementation with only modest effort.
JEqualityGen
Authors: Grech Neville , Rathke Julian , Fischer Bernd 
Published: February 2011

Manually implementing equals (for object comparisons) and hashCode (for object hashing) methods in large software projects is tedious and error-prone. This is due to many special cases, such as field shadowing, comparison between different types, or cyclic object graphs. Here, we present JEqualityGen, a source code generator that automatically derives implementations of these methods.
JEqualityGen proceeds in two states: it first uses source code reflection in MetaAspectJ to generate aspects that contain the method implementations, before it uses weaving on the bytecode level to insert these into the target application. JEqualityGen generates not only correct, but efficient source code that on a typical large-scale Java application exhibits a performance improvement of more than two orders of magnitude in the equality operations generated, compared to an existing system based on runtime reflection. JEqualityGen achieves this by generating runtime profiling code that collects data. This enables it to generate optimised method implementations in a second round.
Targeting the Replication Checkpoint Using SCH 900776, a Potent and Functionally Selective CHK1 Inhibitor Identified via High Content Screening
Authors: Guzi Timothy J. , Paruch Kamil , Dwyer Michael P. , Labroli Marc , Shanahan Frances , Davis Nicole , Taricani Lorena , Wiswell Derek , Seghezzi Wolfgang , Penaflor Ervin , Bhagwat Bhagyashree , Wang Wei , Gu Danling , Hsieh Yunsheng , Lee Suining , Liu Ming , Parry David 
Published: February 2011

Abstract
Checkpoint kinase 1 (CHK1) is an essential serine/threonine kinase that responds to DNA damage and stalled DNA replication. CHK1 is essential for maintenance of replication fork viability during exposure to DNA antimetabolites. In human tumor cell lines, ablation of CHK1 function during antimetabolite exposure led to accumulation of double-strand DNA breaks and cell death. Here, we extend these observations and confirm ablation of CHK2 does not contribute to these phenotypes and may diminish them. Furthermore, concomitant suppression of cyclin-dependent kinase (CDK) activity is sufficient to completely antagonize the desired CHK1 ablation phenotypes. These mechanism-based observations prompted the development of a high-content, cell-based screen for γ-H2AX induction, a surrogate marker for double-strand DNA breaks. This mechanism-based functional approach was used to optimize small molecule inhibitors of CHK1. Specifically, the assay was used to mechanistically define the optimal in-cell profile with compounds exhibiting varying degrees of CHK1, CHK2, and CDK selectivity. Using this approach, SCH 900776 was identified as a highly potent and functionally optimal CHK1 inhibitor with minimal intrinsic antagonistic properties. SCH 900776 exposure phenocopies short interfering RNA-mediated CHK1 ablation and interacts synergistically with DNA antimetabolite agents in vitro and in vivo to selectively induce dsDNA breaks and cell death in tumor cell backgrounds. Mol Cancer Ther; 10(4); 591–602. ©2011 AACR.
Altered Folate Availability Modifies the Molecular Environment of the Human Colorectum: Implications for Colorectal Carcinogenesis
Authors: Protiva Petr , Mason Joel B. , Liu Zhenhua , Hopkins Michael E. , Nelson Celeste , Marshall James R. , Lambrecht Richard W. , Pendyala Swaroop , Kopelovich Levy , Kim Myungjin , Kleinstein Steven H. , Laird Peter W. , Lipkin Martin , Holt Peter R. 
Published: February 2011

Abstract
Low folate status increases colorectal cancer risk. Paradoxically, overly abundant folate supplementation, which is not uncommon in the United States, may increase risk. The mechanisms of these effects are unknown. We conducted two translational studies to define molecular pathways in the human colon altered either by folate supplementation or by dietary folate depletion (followed by repletion). In the first study, 10 healthy, at-risk volunteers (with documented stable/normal folate intake) received supplemental folic acid (1 mg/d) for 8 weeks. In the second study, 10 similar subjects were admitted to a hospital as inpatients for 12 weeks to study folate depletion induced by a low folate diet. A repletion regimen of folic acid (1 mg/d) was provided for the last 4 of these weeks. Both studies included an 8-week run-in period to ensure stabilized folate levels prior to intervention. We obtained 12 rectosigmoid biopsies (from 4 quadrants of normal-appearing mucosa 10–15 cm from the anal verge) at baseline and at measured intervals in both studies for assessing the primary endpoints: genome-wide gene expression, genomic DNA methylation, promoter methylation (depletion/repletion study only), and p53 DNA strand breaks. Serum and rectosigmoid folate concentrations accurately tracked all changes in folate delivery (P &lt; 0.05). In the first study, gene array analysis revealed that supplementation upregulated multiple inflammation- and immune-related pathways in addition to altering several 1-carbon–related enzymes (P &lt; 0.001). In the second study, folate depletion downregulated genes involved in immune response, inflammation, the cell cycle, and mitochondrial/energy pathways; repletion reversed most of these changes. However, changes in gene expression after repletion in the second study (involving immune response and inflammation) did not reach the levels seen after supplementation in the first study. Neither genomic nor promoter-specific DNA methylation changed during the course of the depletion/repletion protocol, and genomic methylation did not change with supplementation in the first study. p53 DNA strand breaks increased with depletion after 12 weeks. In sum, depletion downregulates, whereas repletion or supplementation upregulates pathways related to inflammation and immune response. These findings provide novel support to the concept that excessive folate supplementation might promote colorectal carcinogenesis by enhancing proinflammatory and immune response pathways. These results indicate that modest changes in folate delivery create substantial changes in the molecular milieu of the human colon. Cancer Prev Res; 4(4); 530–43. ©2011 AACR.
Radiometer and Profiler Analysis of the Effects of a Bore and a Solitary Wave on the Stability of the Nocturnal Boundary Layer
Authors: Coleman Timothy A. , Knupp Kevin R. 
Published: February 2011

Abstract
This study uses data from a microwave profiling radiometer (MPR), along with 915-MHz wind profiler, Doppler radar, and surface data to quantify the kinematic and thermodynamic effects of two wave features, an undular bore and a soliton, on the nocturnal boundary layer (NBL) at high temporal resolution. Both wave features passed directly over the MPR and the wind profiler, allowing for detailed analyses. The effects of the wave features on the convective environment are examined, and convective initiation (CI) associated with the wave features is discussed.
The undular bore was illustrated well in Doppler velocity data, and profiler measurements indicated that it produced four wavelengths of upward and downward motion. MPR-derived time–height sections of potential temperature and mixing ratio showed an increase in the depth of the stable boundary layer, along with a decrease in stability, partially associated with mixing of the NBL. The soliton produced a temporary decrease in the depth of the NBL, and also produced destabilization. Trajectory analyses were performed assuming the wave features were two-dimensional, allowing a time-to-space conversion of profiler data. Trajectory analyses, in addition to propagation speed, confirm that the wave features were indeed a bore and a soliton, and that there was vertical divergence in the NBL, likely associated with the decrease in static stability.
MPR data were also used to produce time series of convective parameters, including CAPE, convective inhibition (CIN), and the level of free convection (LFC). The CIN was initially too large for free convection despite sufficient CAPE, but MPR data showed that the CIN decreased by more than 50% upon passage of the bore, and again with the soliton. The waves also decreased the LFC due to cooling above the NBL and slight warming near the surface in the bore. Both the reduction in CIN and the lowering of the LFC made convection more likely. Convective initiation occurred behind both wave features, and the vertical motion provided by the waves may have also aided in this CI.
One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions
Authors: Gobbi Alberto , Karnatzikos Georgios , Scotti Celeste , Mahajan Vivek , Mazzucco Laura , Grigolo Brunella 
Published: February 2011

Objective: The purpose of our study was to determine the effectiveness of cartilage repair utilizing 1-step surgery with bone marrow aspirate concentrate (BMAC) and a collagen I/III matrix (Chondro-Gide, Geistlich, Wolhusen, Switzerland). Materials and Methods: We prospectively followed up for 2 years 15 patients (mean age, 48 years) who were operated for grade IV cartilage lesions of the knee. Six of the patients had multiple chondral lesions; the average size of the lesions was 9.2 cm2. All patients underwent a mini-arthrotomy and concomitant transplantation with BMAC covered with the collagen matrix. Coexisting pathologies were treated before or during the same surgery. X-rays and MRI were collected preoperatively and at 1 and 2 years’ follow-up. Visual analog scale (VAS), International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Marx, SF-36 (physical/mental), and Tegner scores were collected preoperatively and at 6, 12, and 24 months’ follow-up. Four patients gave their consent for second-look arthroscopy and 3 of them for a concomitant biopsy. Results: Patients showed significant improvement in all scores at final follow-up ( P < 0.005). Patients presenting single lesions and patients with small lesions showed higher improvement. MRI showed coverage of the lesion with hyaline-like tissue in all patients in accordance with clinical results. Hyaline-like histological findings were also reported for all the specimens analyzed. No adverse reactions or postoperative complications were noted. Conclusion: This study showed that 1-step surgery with BMAC and collagen I/III matrix could be a viable technique in the treatment of grade IV knee chondral lesions.
Mesenteric lymph node cells from neonates present a prominent IL-12 response to CpG oligodeoxynucleotide via an IL-15 feedback loop of amplification
Authors: Ferret-Bernard Stéphanie , Lacroix-Lamandé Sonia , Remot Aude , Metton Coralie , Bernardet Nelly , Charley Bernard , Drouet Françoise , Laurent Fabrice 
Published: February 2011

Abstract
At birth, the immune system is still in development making neonates more susceptible to infections. The recognition of microbial ligands is a key step in the initiation of immune responses. It can be mimicked to stimulate the immune system by the use of synthetic ligands recognising pattern recognition receptors. In human and mouse, it has been found that neonatal cytokine responses to toll-like receptor (TLR) ligands differ in many ways from those of adults but the relevant studies have been limited to cord blood and spleen cells. In this study, we compared the responses in neonate and adult sheep to CpG oligodeoxynucleotides (ODN), a TLR9 ligand, in both a mucosal and a systemic organ. We observed that in response to CpG-ODN more IL-12 was produced by neonatal than adult sheep cells from mesenteric lymph nodes (MLN) and spleen. This higher IL-12 response was limited to the first 20 days after birth for MLN cells but persisted for a longer period for spleen cells. The major IL-12-producing cells were identified as CD14+CD11b+. These cells were poor producers of IL-12 in response to direct stimulation with CpG-ODN and required the cooperation of other MLN cells. The difference in response to CpG-ODN between neonates and adults can be attributed to both a higher proportion of CD14+CD11b+ cells in neonate lambs and their higher capacity to produce IL-15. The IL-15 increases IL-12 production by an amplifying feedback loop involving CD40.
Tracing the legacy of the early Hainan Islanders - a perspective from mitochondrial DNA
Authors: Peng Min-Sheng , He Jun-Dong , Liu Hai-Xin , Zhang Ya-Ping 
Published: February 2011

AbstractBackgroundHainan Island is located around the conjunction of East Asia and Southeast Asia, and during the Last Glacial Maximum (LGM) was connected with the mainland. This provided an opportunity for the colonization of Hainan Island by modern human in the Upper Pleistocene. Whether the ancient dispersal left any footprints in the contemporary gene pool of Hainan islanders is debatable.ResultsWe collected samples from 285 Li individuals and analyzed mitochondrial DNA (mtDNA) variations of hypervariable sequence I and II (HVS-I and II), as well as partial coding regions. By incorporating previously reported data, the phylogeny of Hainan islanders was reconstructed. We found that Hainan islanders showed a close relationship with the populations in mainland southern China, especially from Guangxi. Haplotype sharing analyses suggested that the recent gene flow from the mainland might play important roles in shaping the maternal pool of Hainan islanders. More importantly, haplogroups M12, M7e, and M7c1* might represent the genetic relics of the ancient population that populated this region; thus, 14 representative complete mtDNA genomes were further sequenced.ConclusionsThe detailed phylogeographic analyses of haplogroups M12, M7e, and M7c1* indicated that the early peopling of Hainan Island by modern human could be traced back to the early Holocene and/or even the late Upper Pleistocene, around 7 - 27 kya. These results correspond to both Y-chromosome and archaeological studies.
The genetic interaction network of CCW12, a Saccharomyces cerevisiae gene required for cell wall integrity during budding and formation of mating projections
Authors: Ragni Enrico , Piberger Heidi , Neupert Christine , García-Cantalejo Jesús , Popolo Laura , Arroyo Javier , Aebi Markus , Strahl Sabine 
Published: February 2011

Abstract

Background
Mannoproteins construct the outer cover of the fungal cell wall. The covalently linked cell wall protein Ccw12p is an abundant mannoprotein. It is considered as crucial structural cell wall component since in baker's yeast the lack of CCW12 results in severe cell wall damage and reduced mating efficiency.

Results
In order to explore the function of CCW12, we performed a Synthetic Genetic Analysis (SGA) and identified genes that are essential in the absence of CCW12. The resulting interaction network identified 21 genes involved in cell wall integrity, chitin synthesis, cell polarity, vesicular transport and endocytosis. Among those are PFD1, WHI3, SRN2, PAC10, FEN1 and YDR417C, which have not been related to cell wall integrity before. We correlated our results with genetic interaction networks of genes involved in glucan and chitin synthesis. A core of genes essential to maintain cell integrity in response to cell wall stress was identified. In addition, we performed a large-scale transcriptional analysis and compared the transcriptional changes observed in mutant ccw12 Δ with transcriptomes from studies investigating responses to constitutive or acute cell wall damage. We identified a set of genes that are highly induced in the majority of the mutants/conditions and are directly related to the cell wall integrity pathway and cell wall compensatory responses. Among those are BCK1, CHS3, EDE1, PFD1, SLT2 and SLA1 that were also identified in the SGA. In contrast, a specific feature of mutant ccw12 Δ is the transcriptional repression of genes involved in mating. Physiological experiments substantiate this finding. Further, we demonstrate that Ccw12p is present at the cell periphery and highly concentrated at the presumptive budding site, around the bud, at the septum and at the tip of the mating projection.

Conclusions
The combination of high throughput screenings, phenotypic analyses and localization studies provides new insight into the function of Ccw12p. A compensatory response, culminating in cell wall remodelling and transport/recycling pathways is required to buffer the loss of CCW12. Moreover, the enrichment of Ccw12p in bud, septum and mating projection is consistent with a role of Ccw12p in preserving cell wall integrity at sites of active growth.
The microarray data produced in this analysis have been submitted to NCBI GEO database and GSE22649 record was assigned.
A clinical trial alert tool to recruit large patient samples and assess selection bias in general practice research
Authors: Heinemann Stephanie , Thüring Sabine , Wedeken Sven , Schäfer Tobias , Scheidt-Nave Christa , Ketterer Mirko , Himmel Wolfgang 
Published: February 2011

Abstract

Background
Many research projects in general practice face problems when recruiting patients, often resulting in low recruitment rates and an unknown selection bias, thus limiting their value for health services research. The objective of the study is to evaluate the recruitment performance of the practice staff in 25 participating general practices when using a clinical trial alert (CTA) tool.

Methods
The CTA tool was developed for an osteoporosis survey of patients at risk for osteoporosis and fractures. The tool used data from electronic patient records (EPRs) to automatically identify the population at risk (net sample), to apply eligibility criteria, to contact eligible patients, to enrol and survey at least 200 patients per practice. The effects of the CTA intervention were evaluated on the basis of recruitment efficiency and selection bias.

Results
The CTA tool identified a net sample of 16,067 patients (range 162 to 1,316 per practice), of which the practice staff reviewed 5,161 (32%) cases for eligibility. They excluded 3,248 patients and contacted 1,913 patients. Of these, 1,526 patients (range 4 to 202 per practice) were successfully enrolled and surveyed. This made up 9% of the net sample and 80% of the patients contacted. Men and older patients were underrepresented in the study population.

Conclusion
Although the recruitment target was unreachable for most practices, the practice staff in the participating practices used the CTA tool successfully to identify, document and survey a large patient sample. The tool also helped the research team to precisely determine a slight selection bias.