bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-Directional Radar Observation for Preliminary Assessment of the Ku-Band Broadband Radar Network
Authors: Yoshikawa Eiichi , Ushio Tomoo , Kawasaki Zen , Chandrasekar V. 
Published: September 2012

Abstract
A short-baseline weather radar network consisting of Ku-band broadband radars (BBR) for meteorological application is under development. The BBR is a short-range and high-resolution Doppler radar for meteorological application, whose range and temporal resolution are several meters and 1 min per volume scan, respectively and coverage is from 50 m to 15 or 20 km. A radar network consisting of BBRs is useful for rapidly and accurately detecting and analyzing small-scale weather phenomena such as localized scattered thunderstorms, tornadoes, and downbursts in locations with a complex topography such as urban or mountainous area. The BBR network project plans to deploy three BBRs in the north Osaka, Japan, area and to observe and analyzing small-scale weather phenomena in detail. At present, two functioning BBRs have been deployed in the Osaka area. This paper presents a description of the BBR network project and its preliminary assessment. Observations of the two-BBR test bed derive expected properties of the three-BBR network, which efficiently covers troposphere in the overlapped area with a minimum observable altitude of tens of meters and a sensitivity of 10.2 dBZ (spatial average at a 5000-km altitude). Integrated reflectivity and preliminary algorithm for multiradar products in the two-BBR test bed, presenting a promising fine structure of precipitation cells, is also shown.
An Upwind-Biased Transport Scheme Using a Quadratic Reconstruction on Spherical Icosahedral Grids
Authors: Miura Hiroaki , Skamarock William C. 
Published: September 2012

Abstract
Several transport schemes developed for spherical icosahedral grids are based on the piecewise linear approximation. The simplest one among them uses an algorithm where the tracer distribution in the upwind side of a cell face is reconstructed using a linear surface. Recently, it was demonstrated that using second- or fourth-order reconstructions instead of the linear one produces better results. The computational cost of the second-order reconstruction method was not much larger than the linear one, while that of the fourth-order one was significantly larger. In this work, the authors propose another second-order reconstruction scheme on the spherical icosahedral grids, motivated by some ideas from the piecewise parabolic method. The second-order profile of a tracer is reconstructed under two constraints: (i) the area integral of the profile is equal to the cell-averaged value times the cell area and (ii) the profile is the least squares fit to the cell-vertex values. The new scheme [the second upwind-biased quadratic approximation (UQA-2)] is more accurate than the preceding second-order reconstruction scheme [the first upwind-biased quadratic approximation (UQA-1)] in most of the tests in this work. Solutions of UQA-2 are sharper than those of UQA-1, although with slightly larger phase errors. The computational cost of UQA-2 is comparable to UQA-1.
Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing
Authors: Dolnik Anna , Engelmann Julia C. , Scharfenberger-Schmeer Maren , Mauch Julian , Kelkenberg-Schade Sabine , Haldemann Berit , Fries Tamara , Krönke Jan , Kühn Michael W. M. , Paschka Peter , Kayser Sabine , Wolf Stephan , Gaidzik Verena I. , Schlenk Richard F. , Rücker Frank G. , Döhner Hartmut , Lottaz Claudio , Döhner Konstanze , Bullinger Lars 
Published: September 2012

Abstract
Acute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (∼ 3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were nonrecurrent, we observed an enrichment of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A, and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2, and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the nonclassic regulators of mRNA processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a large number of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML.
Loss of kindlin-3 alters the threshold for NK cell activation in human leukocyte adhesion deficiency-III
Authors: Gruda Raizy , Brown Alice C. N. , Grabovsky Valentin , Mizrahi Saar , Gur Chamutal , Feigelson Sara W. , Achdout Hagit , Bar-on Yotam , Alon Ronen , Aker Memet , Davis Daniel M. , Mandelboim Ofer 
Published: September 2012

Abstract
Recent evidence suggests that kindlin-3 is a major coactivator, required for most, if not all, integrin activities. Here we studied the function of kindlin-3 in regulating NK cell activation by studying a patient with kindlin-3 deficiency (leukocyte adhesion deficiency-III). We found that kindlin-3 is required for NK cell migration and adhesion under shear force. Surprisingly, we also found that kindlin-3 lowers the threshold for NK cell activation. Loss of kindlin-3 has a pronounced effect on NK cell–mediated cytotoxicity triggered by single activating receptors. In contrast, for activation through multiple receptors, kindlin-3 deficiency is overcome and target cells killed. The realization that NK cell activity is impaired, but not absent in leukocyte adhesion deficiency, may lead to the development of more efficient therapy for this rare disease.
Cytokine activation induces human memory-like NK cells
Authors: Romee Rizwan , Schneider Stephanie E. , Leong Jeffrey W. , Chase Julie M. , Keppel Catherine R. , Sullivan Ryan P. , Cooper Megan A. , Fehniger Todd A. 
Published: September 2012

Abstract
Natural killer (NK) cells are lymphocytes that play an important role in the immune response to infection and malignancy. Recent studies in mice have shown that stimulation of NK cells with cytokines or in the context of a viral infection results in memory-like properties. We hypothesized that human NK cells exhibit such memory-like properties with an enhanced recall response after cytokine preactivation. In the present study, we show that human NK cells preactivated briefly with cytokine combinations including IL-12, IL-15, and IL-18 followed by a 7- to 21-day rest have enhanced IFN-γ production after restimulation with IL-12 + IL-15, IL-12 + IL-18, or K562 leukemia cells. This memory-like phenotype was retained in proliferating NK cells. In CD56dim NK cells, the memory-like IFN-γ response was correlated with the expression of CD94, NKG2A, NKG2C, and CD69 and a lack of CD57 and KIR. Therefore, human NK cells have functional memory-like properties after cytokine activation, which provides a novel rationale for integrating preactivation with combinations of IL-12, IL-15, and IL-18 into NK cell immunotherapy strategies.
IS-seq: a novel high throughput survey of in vivo IS6110 transposition in multiple Mycobacterium tuberculosis genomes
Authors: Reyes Alejandro , Sandoval Andrea , Cubillos-Ruiz Andrés , Varley Katherine E , Hernández-Neuta Ivan , Samper Sofía , Martín Carlos , García María Jesús , Ritacco Viviana , López Lucelly , Robledo Jaime , Zambrano María Mercedes , Mitra Robi D , Del Portillo Patricia 
Published: September 2012

Abstract

Background
The insertion element IS6110 is one of the main sources of genomic variability in Mycobacterium tuberculosis, the etiological agent of human tuberculosis. Although IS 6110 has been used extensively as an epidemiological marker, the identification of the precise chromosomal insertion sites has been limited by technical challenges. Here, we present IS-seq, a novel method that combines high-throughput sequencing using Illumina technology with efficient combinatorial sample multiplexing to simultaneously probe 519 clinical isolates, identifying almost all the flanking regions of the element in a single experiment.

Results
We identified a total of 6,976 IS6110 flanking regions on the different isolates. When validated using reference strains, the method had 100% specificity and 98% positive predictive value. The insertions mapped to both coding and non-coding regions, and in some cases interrupted genes thought to be essential for virulence or in vitro growth. Strains were classified into families using insertion sites, and high agreement with previous studies was observed.

Conclusions
This high-throughput IS-seq method, which can also be used to map insertions in other organisms, extends previous surveys of in vivo interrupted loci and provides a baseline for probing the consequences of disruptions in M. tuberculosis strains.
Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains
Authors: Parsons Michael J , Grimm Christina , Paya-Cano Jose L , Fernandes Cathy , Liu Lin , Philip Vivek M , Chesler Elissa J , Nietfeld Wilfried , Lehrach Hans , Schalkwyk Leonard C 
Published: September 2012

AbstractBackgroundmiRNAs are short single-stranded non-coding RNAs involved in post-transcriptional gene regulation that play a major role in normal biological functions and diseases. Little is currently known about how expression of miRNAs is regulated. We surveyed variation in miRNA abundance in the hippocampus of mouse inbred strains, allowing us to take a genetic approach to the study of miRNA regulation, which is novel for miRNAs. The BXD recombinant inbred panel is a very well characterized genetic reference panel which allows quantitative trait locus (QTL) analysis of miRNA abundance and detection of correlates in a large store of brain and behavioural phenotypes.ResultsWe found five suggestivetransQTLs for the regulation of miRNAs investigated. Further analysis of these QTLs revealed two genes,TnikandPhf17,under themiR-212regulatory QTLs, whose expression levels were significantly correlated with miR-212 expression. We found that miR-212 expression is correlated with cocaine-related behaviour, consistent with a reported role for this miRNA in the control of cocaine consumption. miR-31 is correlated with anxiety and alcohol related behaviours. KEGG pathway analysis of each miRNA’s expression correlates revealed enrichment of pathways including MAP kinase, cancer, long-term potentiation, axonal guidance and WNT signalling.ConclusionsThe BXD reference panel allowed us to establish genetic regulation and characterize biological function of specific miRNAs. QTL analysis enabled detection of genetic loci that regulate the expression of these miRNAs. eQTLs that regulate miRNA abundance are a new mechanism by which genetic variation influences brain and behaviour. Analysis of one of these QTLs revealed a gene,Tnik,which may regulate the expression of a miRNA, a molecular pathway and a behavioural phenotype. Evidence of genetic covariation of miR-212 abundance and cocaine related behaviours is strongly supported by previous functional studies, demonstrating the value of this approach for discovery of new functional roles and downstream processes regulated by miRNA.
Whole transcriptome analysis of a reversible neurodegenerative process in Drosophila reveals potential neuroprotective genes
Authors: Ferreiro María José , Rodríguez-Ezpeleta Naiara , Pérez Coralia , Hackenberg Michael , Aransay Ana María , Barrio Rosa , Cantera Rafael 
Published: September 2012

Abstract

Background
Neurodegenerative diseases are progressive and irreversible and they can be initiated by mutations in specific genes. Spalt-like genes (Sall) encode transcription factors expressed in the central nervous system. In humans, SALL mutations are associated with hereditary syndromes characterized by mental retardation, sensorineural deafness and motoneuron problems, among others. Drosophila sall mutants exhibit severe neurodegeneration of the central nervous system at embryonic stage 16, which surprisingly reverts later in development at embryonic stage 17, suggesting a potential to recover from neurodegeneration. We hypothesize that this recovery is mediated by a reorganization of the transcriptome counteracting SALL lost. To identify genes associated to neurodegeneration and neuroprotection, we used mRNA-Seq to compare the transcriptome of Drosophila sall mutant and wild type embryos from neurodegeneration and reversal stages.

Results
Neurodegeneration stage is associated with transcriptional changes in 220 genes, of which only 5% were already described as relevant for neurodegeneration. Genes related to the groups of Redox, Lifespan/Aging and Mitochondrial diseases are significantly represented at this stage. By contrast, neurodegeneration reversal stage is associated with significant changes in 480 genes, including 424 not previously associated with neuroprotection. Immune response and Salt stress are the most represented groups at this stage.

Conclusions
We identify new genes associated to neurodegeneration and neuroprotection by using an mRNA-Seq approach. The strong homology between Drosophila and human genes raises the possibility to unveil novel genes involved in neurodegeneration and neuroprotection also in humans.
An atypical case of neuronal ceroid lipofuscinosis with co-inheritance of a variably penetrant POLG1mutation
Authors: Staropoli John F , Xin Winnie , Barone Rosemary , Cotman Susan L , Sims Katherine B 
Published: September 2012

Abstract

Background
The neuronal ceroid lipofuscinoses (NCLs, or Batten disease) comprise the most common Mendelian form of childhood-onset neurodegeneration, but the functions of the known underlying gene products remain poorly understood. The clinical heterogeneity of these disorders may shed light on genetic interactors that modify disease onset and progression.

Case presentation
We describe a proband with congenital hypotonia and an atypical form of infantile-onset, biopsy-proven NCL. Pathologic and molecular work-up of this patient identified CLN5 mutations as well as a mutation―previously described as incompletely penetrant or a variant of unknown significance―in POLG1, a nuclear gene essential for maintenance of mitochondrial DNA (mtDNA) copy number. The congenital presentation of this patient is far earlier than that described for either CLN5 patients or affected carriers of the POLG1 variant (c.1550 G > T, p.Gly517Val). Assessment of relative mtDNA copy number and mitochondrial membrane potential in the proband and control subjects suggested a pathogenic effect of the POLG1 change as well as a possible functional interaction with CLN5 mutations.

Conclusions
These findings suggest that an incompletely penetrant variant in POLG1 may modify the clinical phenotype in a case of CLN5 and are consistent with emerging evidence of interactions between NCL-related genes and mitochondrial physiology.
Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis
Authors: Goc Anna , Kochuparambil Samith T , Al-Husein Belal , Al-Azayzih Ahmad , Mohammad Shuaib , Somanath Payaningal R 
Published: September 2012

Abstract

Background
Recent studies suggest the potential benefits of statins as anti-cancer agents. Mechanisms by which statins induce apoptosis in cancer cells are not clear. We previously showed that simvastatin inhibit prostate cancer cell functions and tumor growth. Molecular mechanisms by which simvastatin induce apoptosis in prostate cancer cells is not completely understood.

Methods
Effect of simvastatin on PC3 cell apoptosis was compared with docetaxel using apoptosis, TUNEL and trypan blue viability assays. Protein expression of major candidates of the intrinsic pathway downstream of simvastatin-mediated Akt inactivation was analyzed. Gene arrays and western analysis of PC3 cells and tumor lysates were performed to identify the candidate genes mediating extrinsic apoptosis pathway by simvastatin.

Results
Data indicated that simvastatin inhibited intrinsic cell survival pathway in PC3 cells by enhancing phosphorylation of Bad, reducing the protein expression of Bcl-2, Bcl-xL and cleaved caspases 9/3. Over-expression of PC3 cells with Bcl-2 or DN-caspase 9 did not rescue the simvastatin-induced apoptosis. Simvastatin treatment resulted in increased mRNA and protein expression of molecules such as TNF, Fas-L, Traf1 and cleaved caspase 8, major mediators of intrinsic apoptosis pathway and reduced protein levels of pro-survival genes Lhx4 and Nme5.

Conclusions
Our study provides the first report that simvastatin simultaneously modulates intrinsic and extrinsic pathways in the regulation of prostate cancer cell apoptosis in vitro and in vivo, and render reasonable optimism that statins could become an attractive anti-cancer agent.
Neck/shoulder pain and low back pain among school teachers in China, prevalence and risk factors
Authors: Yue Pengying , Liu Fengying , Li Liping 
Published: September 2012

Abstract

Background
School teachers represent an occupational group among which there appears to be a high prevalence of neck and/or shoulder pain (NSP) and low back pain (LBP). Epidemiological data on NSP and LBP in Chinese teachers are limited. The aim of this study was to investigate the prevalence of and risk factors for NSP and LBP among primary, secondary and high school teachers.

Methods
In a cross-sectional study of teachers from 7 schools, information on participant demographics, work characteristics, occupational factors and musculoskeletal symptoms and pain were collected.

Results
Among 893 teachers, the prevalence of NSP and LBP was 48.7% and 45.6% respectively. There was significant association between the level and prevalence of NSP and LBP among teachers in different schools. The prevalence of NSP among female teachers was much higher than that for males. Self-reported NSP was associated with physical exercise (OR 0.55, 95% CI 0.35 to 0.86), prolonged standing (1.74, 1.03 to 2.95), sitting (1.76, 1.23 to 2.52) and static posture (2.25, 1.56 to 3.24), and uncomfortable back support (1.77, 1.23 to 2.55). LBP was more consistently associated with twisting posture (1.93, 1.30 to 2.87), uncomfortable back support (1.62, 1.13 to 2.32) and prolonged sitting (1.42, 1.00 to 2.02) and static posture (1.60, 1.11 to 2.31).

Conclusions
NSP and LBP are common among teachers. There were strong associations with different individual, ergonomic, and occupational factors.
Quality of life predicts survival in patients with non-small cell lung cancer
Authors: Li Tsai-Chung , Li Chia-Ing , Tseng Chun-Hua , Lin Kuan-Shin , Yang Sing-Yu , Chen Chih-Yi , Hsia Te-Chun , Lee Yih-Dar , Lin Cheng-Chieh 
Published: September 2012

Abstract

Background
Patients with non-small cell lung cancer (NSCLC) have a poor prognosis. The objective of this study was to examine the relationship of EORTC QLQ-C30 and QLQ-LC13 and survival in patients with NSCLC undergoing different treatments.

Methods
Investigators conducted a health-related quality of life (HRQOL) survey of 488 patients with NSCLC: 162 patients undergoing surgery, 312 patients without surgery, and their survival status was prospectively followed up. EORTC QLQ-C30 and QLQ-LC13 scores and clinical variables at baseline were analyzed using Cox’s proportional hazard regression to identify factors that influenced survival.

Results
Median survival of these 474 patients was 9.82 months. After adjustment, emotional functioning scale, and symptom scales of pain and nausea/vomiting are associated with survival in NSCLC patients with surgery whereas social functioning scale, and symptom scales for fatigue, appetite loss, and financial problems had a significant impact on survival in NSCLC patients without surgery. The results of multivariate analysis showed that none of QLQ-LC13 scales are significant predictors of survival. After simultaneously considering these scales, we found significant independent predictors of survival were nausea/vomiting (HR = 0.11, 95% CI = 0.02-0.63 for score >0 compared with =0) in NSCLC patients with surgery and appetite loss (HR = 1.77, 95% CI = 1.26-2.49 for score >0 compared with =0) in NSCLC patients without surgery.

Conclusions
HRQOL provides additional predictive information that supplements traditional clinical factors, and is a new prognostic indicator for survival of NSCLC patients under different treatments.
Production of copolyesters of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates by E. coli containing an optimized PHA synthase gene
Authors: Gao Xue , Yuan Xiao-Xi , Shi Zhen-Yu , Guo Ying-Ying , Shen Xiao-Wen , Chen Jin-Chun , Wu Qiong , Chen Guo-Qiang 
Published: September 2012

Abstract

Background
Microbial polyhydroxyalkanoates (PHA) are biopolyesters consisting of diverse monomers. PHA synthase PhaC2Ps cloned from Pseudomonas stutzeri 1317 is able to polymerize short-chain-length (scl) 3-hydroxybutyrate (3HB) monomers and medium-chain-length (mcl) 3-hydroxyalkanoates (3HA) with carbon chain lengths ranging from C6 to C12. However, the scl and mcl PHA production in Escherichia coli expressing PhaC2Ps is limited with very low PHA yield.

Results
To improve the production of PHA with a wide range of monomer compositions in E. coli, a series of optimization strategies were applied on the PHA synthase PhaC2Ps. Codon optimization of the gene and mRNA stabilization with a hairpin structure were conducted and the function of the optimized PHA synthase was tested in E. coli. The transcript was more stable after the hairpin structure was introduced, and western blot analysis showed that both codon optimization and hairpin introduction increased the protein expression level. Compared with the wild type PhaC2Ps, the optimized PhaC2Ps increased poly-3-hydroxybutyrate (PHB) production by approximately 16-fold to 30% of the cell dry weight. When grown on dodecanoate, the recombinant E. coli harboring the optimized gene phaC2

Ps

O with a hairpin structure in the 5’ untranslated region was able to synthesize 4-fold more PHA consisting of 3HB and medium-chain-length 3HA compared to the recombinant harboring the wild type phaC2

Ps
.

Conclusions
The levels of both PHB and scl-mcl PHA in E. coli were significantly increased by series of optimization strategies applied on PHA synthase PhaC2Ps. These results indicate that strategies including codon optimization and mRNA stabilization are useful for heterologous PHA synthase expression and therefore enhance PHA production.