bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Framework to Select Clinically Relevant Cancer Cell Lines for Investigation by Establishing Their Molecular Similarity with Primary Human Cancers
Authors: Dancik Garrett M. , Ru Yuanbin , Owens Charles R. , Theodorescu Dan 
Published: October 2011

Abstract
Experimental work on human cancer cell lines often does not translate to the clinic. We posit that this is because some cells undergo changes in vitro that no longer make them representative of human tumors. Here, we describe a novel alignment method named Spearman's rank correlation classification method (SRCCM) that measures similarity between cancer cell lines and human tumors via gene expression profiles, for the purpose of selecting lines that are biologically relevant. To show utility, we used SRCCM to assess similarity of 36 bladder cancer lines with 10 epithelial human tumor types (N = 1,630 samples) and with bladder tumors of different stages and grades (N = 144 samples). Although 34 of 36 lines aligned to bladder tumors rather than other histologies, only 16 of 28 had SRCCM assigned grades identical to that of their original source tumors. To evaluate the clinical relevance of this approach, we show that gene expression profiles of aligned cell lines stratify survival in an independent cohort of 87 bladder patients (HR = 3.41, log-rank P = 0.0077) whereas unaligned cell lines using original tumor grades did not. We repeated this process on 22 colorectal cell lines and found that gene expression profiles of 17 lines aligning to colorectal tumors and selected based on their similarity with 55 human tumors stratified survival in an independent cohort of 177 colorectal cancer patients (HR = 2.35, log-rank P = 0.0019). By selecting cell lines that reflect human tumors, our technique promises to improve the clinical translation of laboratory investigations in cancer. Cancer Res; 71(24); 7398–409. ©2011 AACR.
Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin
Authors: Horvath Gabriella A , Selby Kathryn , Poskitt Ken , Hyland Keith , Waters Paula J , Coulter-Mackie Marion , Stockler-Ipsiroglu Sylvia G 
Published: October 2011

Background: Serotonin has an important role in vascular resistance and blood pressure control, and a functional serotonin transporter polymorphism has been associated with migraine. Disturbances in serotonin metabolism have been associated with autism, depression, and myoclonus related conditions, but serotonin has far more functions in the body. Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura in which attacks are associated with hemiparesis. Cases: We present two siblings with hemiplegic migraine, depression, progressive spastic paraparesis, myelopathy, and spinal cord atrophy. One of the sisters presented with prolonged coma after a migraine episode. Both sisters were found to have low cerebrospinal fluid serotonin metabolite (5-hydroxyindoleacetic acid), low platelet serotonin levels, and diminished serotonin transport capacity. Their clinical symptoms improved on 5-hydroxytryptophan replacement therapy. Mutational analysis of the CACNA1A and ATP1A2 genes was negative. Conclusion: This is the first time that systemic serotonin deficiency has been described in familial hemiplegic migraine. We hypothesize that the deficiency of serotonin transport may be part of a complex cellular membrane trafficking dysfunction involving not only the serotonin transporter but also other transporters and ion channels.
Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype
Authors: Grossmann Vera , Tiacci Enrico , Holmes Antony B. , Kohlmann Alexander , Martelli Maria Paola , Kern Wolfgang , Spanhol-Rosseto Ariele , Klein Hans-Ulrich , Dugas Martin , Schindela Sonja , Trifonov Vladimir , Schnittger Susanne , Haferlach Claudia , Bassan Renato , Wells Victoria A. , Spinelli Orietta , Chan Joseph , Rossi Roberta , Baldoni Stefano , De Carolis Luca , Goetze Katharina , Serve Hubert , Peceny Rudolf , Kreuzer Karl-Anton , Oruzio Daniel , Specchia Giorgina , Di Raimondo Francesco , Fabbiano Francesco , Sborgia Marco , Liso Arcangelo , Farinelli Laurent , Rambaldi Alessandro , Pasqualucci Laura , Rabadan Raul , Haferlach Torsten , Falini Brunangelo 
Published: October 2011

AbstractAmong acute myeloid leukemia (AML) patients with a normal karyotype (CN-AML), NPM1 and CEBPA mutations define World Health Organization 2008 provisional entities accounting for approximately 60% of patients, but the remaining 40% are molecularly poorly characterized. Using whole-exome sequencing of one CN-AML patient lacking mutations in NPM1, CEBPA, FLT3-ITD, IDH1, and MLL-PTD, we newly identified a clonal somatic mutation in BCOR (BCL6 corepressor), a gene located on chromosome Xp11.4. Further analyses of 553 AML patients showed that BCOR mutations occurred in 3.8% of unselected CN-AML patients and represented a substantial fraction (17.1%) of CN-AML patients showing the same genotype as the AML index patient subjected to whole-exome sequencing. BCOR somatic mutations were: (1) disruptive events similar to the germline BCOR mutations causing the oculo-facio-cardio-dental genetic syndrome; (2) associated with decreased BCOR mRNA levels, absence of full-length BCOR, and absent or low expression of a truncated BCOR protein; (3) virtually mutually exclusive with NPM1 mutations; and (4) frequently associated with DNMT3A mutations, suggesting cooperativity among these genetic alterations. Finally, BCOR mutations tended to be associated with an inferior outcome in a cohort of 422 CN-AML patients (25.6% vs 56.7% overall survival at 2 years; P = .032). Our results for the first time implicate BCOR in CN-AML pathogenesis.
A modified Stokes-Einstein equation for Aβ aggregation
Authors: Achuthan Srisairam , Chung Bong Jae , Ghosh Preetam , Rangachari Vijayaraghavan , Vaidya Ashwin 
Published: October 2011

Abstract

Background
In all amyloid diseases, protein aggregates have been implicated fully or partly, in the etiology of the disease. Due to their significance in human pathologies, there have been unprecedented efforts towards physiochemical understanding of aggregation and amyloid formation over the last two decades. An important relation from which hydrodynamic radii of the aggregate is routinely measured is the classic Stokes-Einstein equation. Here, we report a modification in the classical Stokes-Einstein equation using a mixture theory approach, in order to accommodate the changes in viscosity of the solvent due to the changes in solute size and shape, to implement a more realistic model for Aβ aggregation involved in Alzheimer’s disease. Specifically, we have focused on validating this model in protofibrill lateral association reactions along the aggregation pathway, which has been experimentally well characterized.

Results
The modified Stokes-Einstein equation incorporates an effective viscosity for the mixture consisting of the macromolecules and solvent where the lateral association reaction occurs. This effective viscosity is modeled as a function of the volume fractions of the different species of molecules. The novelty of our model is that in addition to the volume fractions, it incorporates previously published reports on the dimensions of the protofibrils and their aggregates to formulate a more appropriate shape rather than mere spheres. The net result is that the diffusion coefficient which is inversely proportional to the viscosity of the system is now dependent on the concentration of the different molecules as well as their proper shapes. Comparison with experiments for variations in diffusion coefficients over time reveals very similar trends.

Conclusions
We argue that the standard Stokes-Einstein’s equation is insufficient to understand the temporal variations in diffusion when trying to understand the aggregation behavior of Aβ 42 proteins. Our modifications also involve inclusion of improved shape factors of molecules and more appropriate viscosities. The modification we are reporting is not only useful in Aβ aggregation but also will be important for accurate measurements in all protein aggregation systems.
Latent Semantic Indexing of PubMed abstracts for identification of transcription factor candidates from microarray derived gene sets
Authors: Roy Sujoy , Heinrich Kevin , Phan Vinhthuy , Berry Michael W , Homayouni Ramin 
Published: October 2011

Abstract

Background
Identification of transcription factors (TFs) responsible for modulation of differentially expressed genes is a key step in deducing gene regulatory pathways. Most current methods identify TFs by searching for presence of DNA binding motifs in the promoter regions of co-regulated genes. However, this strategy may not always be useful as presence of a motif does not necessarily imply a regulatory role. Conversely, motif presence may not be required for a TF to regulate a set of genes. Therefore, it is imperative to include functional (biochemical and molecular) associations, such as those found in the biomedical literature, into algorithms for identification of putative regulatory TFs that might be explicitly or implicitly linked to the genes under investigation.

Results
In this study, we present a Latent Semantic Indexing (LSI) based text mining approach for identification and ranking of putative regulatory TFs from microarray derived differentially expressed genes (DEGs). Two LSI models were built using different term weighting schemes to devise pair-wise similarities between 21,027 mouse genes annotated in the Entrez Gene repository. Amongst these genes, 433 were designated TFs in the TRANSFAC database. The LSI derived TF-to-gene similarities were used to calculate TF literature enrichment p-values and rank the TFs for a given set of genes. We evaluated our approach using five different publicly available microarray datasets focusing on TFs Rel, Stat6, Ddit3, Stat5 and Nfic. In addition, for each of the datasets, we constructed gold standard TFs known to be functionally relevant to the study in question. Receiver Operating Characteristics (ROC) curves showed that the log-entropy LSI model outperformed the tf-normal LSI model and a benchmark co-occurrence based method for four out of five datasets, as well as motif searching approaches, in identifying putative TFs.

Conclusions
Our results suggest that our LSI based text mining approach can complement existing approaches used in systems biology research to decipher gene regulatory networks by providing putative lists of ranked TFs that might be explicitly or implicitly associated with sets of DEGs derived from microarray experiments. In addition, unlike motif searching approaches, LSI based approaches can reveal TFs that may indirectly regulate genes.
Immunodominant proteins α-1 giardin and β-giardin are expressed in both assemblages A and B of Giardia lamblia
Authors: Feliziani Constanza , Merino María C , Rivero María R , Hellman Ulf , Pistoresi-Palencia María C , Rópolo Andrea S 
Published: October 2011

Abstract

Background
To date, eight assemblages of Giardia lamblia have been described, but only assemblages A and B are known to infect humans. Despite the fact that the genomic, biological, and clinical differences found between these two assemblages has raised the possibility that they may be considered different species, there is relatively limited information on their phenotypic differences. In the present study, we developed monoclonal antibodies against alpha-1 and beta giardin, two immunodominant proteins produced during G. lamblia infection, and studied their expression and localization in WB (assemblage A) and GS trophozoites (assemblage B).

Results
The polyclonal antibodies generated against WB trophozoites, particularly those recognizing intracellular proteins as well as the proteins present at the plasma membrane (variable-specific surface proteins), showed cross-reactivity with intracellular proteins in GS trophozoites. The use of monoclonal antibodies against beta giardin indicated ventral disc localization, particularly at the periphery in WB trophozoites. Interestingly, although beta giardin was also restricted to the ventral disc in GS trophozoites, the pattern of localization clearly differed in this assemblage. On the other hand, monoclonal antibodies against alpha-1 giardin showed plasma membrane localization in both assemblages with the bare area of GS trophozoites also being distinguished. Moreover, the same localization at the plasma membrane was observed in Portland-1 (Assemblage A) and in P15 (Assemblage E) trophozoites.

Conclusions
We found differences in localization of the beta giardin protein between assemblages A and B, but the same pattern of localization of alpha-1 giardin in strains from Assemblages A, B and E. These findings reinforce the need for more studies based on phenotypic characteristics in order to disclose how far one assemblage is from the other.
CBG Santiago: A Novel CBG Mutation
Authors: Torpy D. J. , Lundgren B. Ardesjö , Ho J. T. , Lewis J. G. , Scott H. S. , Mericq V. 
Published: October 2011

Context:
Corticosteroid-binding globulin (CBG; SERPIN A6) gene mutations are rare; only four mutations have been described, often in association with fatigue and chronic pain, albeit with incomplete penetrance.

Patient:
We report a kindred with a novel SERPINA6 mutation. The proband, a 9-yr-old male, had excessive postexertional fatigue, weakness, and migraine.

Main Outcome Measures and Results:
Investigations revealed low morning and ACTH-stimulated peak cortisol levels. SERPIN A6 sequencing detected a novel exon 2 single base deletion (c.13delC) leading to a frameshift generating a stop codon within the signal peptide coding region (p.Leu5CysfsX26) and 50% reduced CBG levels in heterozygotes. The patient's father and two sisters share the mutation. Symptom expression within the family may have been modified by a polymorphic CBG allele (c.735G&gt;T). Exogenous hydrocortisone had no effect on the fatigue.

Conclusion:
This report documents the fifth CBG gene mutation in humans and the second causing major effects on CBG levels. Individuals with low CBG levels may be misdiagnosed as having secondary hypocortisolism. The association with fatigue and idiopathic pain is again noted and may relate to altered stress system function. Variability of the phenotype may relate to other genetic variations of the CBG gene or environmental factors.
The Combination of Purified Recombinant Human Platelet‐Derived Growth Factor‐BB and Equine Particulate Bone Graft for Periodontal Regeneration
Authors: Nevins Myron , Nevins Marc L. , Karimbux Nadeem , Kim Soo‐Woo , Schupbach Peter , Kim David M. 
Published: October 2011

Background: The objective of this study is to evaluate the potential for periodontal regeneration of a critical‐sized defect with the application of recombinant human platelet‐derived growth factor (rhPDGF‐BB) combined with either a particulate equine or a β‐tricalcium phosphate (β‐TCP) matrix.Methods: Critical‐sized intrabony 2‐wall defects were created bilaterally on the distal surface of the second premolar and the mesial surface of the first molar in nine hounds. Twelve defects received rhPDGF‐BB/equine treatment, 12 defects received rhPDGF‐BB/β‐TCP treatment, and the remaining 12 sites served as sham‐surgery controls. The animals were sacrificed after a 10‐week healing period.Results: Clinical healing was uneventful without obvious signs of overt gingival inflammation. Histologic and histomorphometric analyses revealed statistically that there were differences among the three groups in terms of new bone formation (P <0.001). The amount of test material for both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP groups was comparable, but the amount of newly formed bone was significantly higher (P <0.01) in favor of the rhPDGF‐BB/equine group. The amount of new cementum formed for the rhPDGF‐BB/equine group (4.8 ± 1.3 mm) was significantly higher (P =0.001) than the sham‐surgery control group (1.7 ± 1.9 mm).Conclusion: Both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP have the potential to support the regeneration of the periodontal attachment apparatus.
Hunter New England Training (HNET): How to Effect Culture Change in a Psychiatry Medical Workforce
Authors: Cohen Martin , Llewellyn Anthony , Ditton-Phare Philippa , Sandhu Harsimrat , Vamos Marina 
Published: October 2011

Objective: It is now recognized that education and training are at the core of quality systems in health care. In this paper we discuss the processes and drivers that underpinned the development of high quality education and training programs and placements for all junior doctors. The early identification and development of doctors interested in psychiatry as a career, engagement and co-operation with the broader junior doctor network and the creation of teaching opportunities for trainees that was linked to their stage of development were identified as key to the success of the program. Conclusions: Targeted, high quality education programs and clinical placements coupled with strategic development of workforce has reduced staff turn over, led to the stabilization of the medical workforce and created a culture where learning and supervision are highly valued.
Obtaining high formability of IF-galvanized steel tailor welded blanks by applying optimum CO2 laser welding parameters
Authors: Abbasi M. , Ketabchi M. , Shakeri H. R. , Shafaat M. A. 
Published: October 2011

Abstract
Tailor welded blanks are complex component designs tailor-made through welding of multiple metal sheets with different thicknesses, shapes and/or strengths prior to forming. Making tailor welded blanks out of interstitial free galvanized steels not only provides the general advantages of tailor blanks including the weight and manufacturing cost reductions per part, but also considering the properties of the parent sheet, could guarantee exceptional corrosion resistance as well as favorable formability characteristics. The quality of the weld joint in these blanks and their formability is directly influenced by the parameters of the welding process. In this research, the use of CO2 laser for welding thin interstitial free galvanized steel sheets with different thicknesses (0.8 and 1.2 mm) was optimized using the Taguchi analytical methodology. The welding parameters including the shielding gas pressure, laser power and travel speed of the laser beam were evaluated by measuring the dome height value after forming and the optimal welding parameters values were obtained. The optimal result was equated with the highest dome height value and consequently highest formability. Results showed that the welding parameters have a great effect on achievable properties of tailor welded blanks and entrapment of zinc vapor due to evaporation of zinc has a significant role in determining the weld quality of the studied blanks. Microstructure, hardness and mechanical properties of different welds were also investigated. Formation of voids and porosity as well as lack of diffusion were some of the results of welding with non-optimized parameters. An equation based on a regression model is presented to predict the minimum dome height value of tailor welded blank consisted of interstitial free galvanized steels with a thickness ratio of 1.5.
Magnetic properties of Co0.5Zn0.5Fe2O4 nanopowders prepared by means of the template-assisted hydrothermal method
Authors: Shen Q. , He H. Y. 
Published: October 2011

Abstract
In the present article, nickel cobalt ferrite (Co0.5Zn0.5Fe2O4) nanoparticles were synthesized using a template-assisted hydrothermal method. Carboxymethyl cellulose was used as the templating agent for controlling the morphology of the Co0.5Zn0.5Fe2O4 nanoparticles. The synthesized nanoparticles were characterized using X-ray diffraction, scanning electron microscopy, and a vibrating sample magnetometer. The results indicated that the morphology of the nanoparticles changed from granular and superparamagnetic to platelike and ferromagnetic with the addition of the template. The Co0.5Zn0.5Fe2O4 nanoparticles synthesized without the template exhibited a saturation magnetization and coercivity 2.81 T and 0.2 kA · m– 1, while when the template was used, the saturation magnetization and coercivity increased to 3.13 T and 76.6 kA · m– 1 as the template proportion increased to 0.3.
Isolation of polymorphic microsatellite markers and tests of cross‐amplification in four widespread European calcicole ferns
Authors: de Groot G. Arjen , Korpelainen Helena , Wubs E. R. Jasper , Erkens Roy 
Published: October 2011

• Premise of the study:Studies on the biogeography and population genetics of the widespread European rock ferns Asplenium scolopendrium, A. trichomanessubsp. quadrivalens, Polystichum setiferum, and P. aculeatumwould potentially yield interesting new insights into the colonization capacities of ferns. Markers with sufficient resolution for detailed genetic studies are, however, not yet available.• Methods and Results:Using genome screening with intersimple sequence repeat (ISSR) primers, a total of 16 different microsatellite markers were isolated and characterized for the four species. Some of these markers could be exchanged within each congeneric pair.• Conclusions:The developed primer sets will be very useful for analyses of the biogeography and population genetics of some widespread calcicole ferns. The observed cross‐amplification rates suggest a high potential for application on additional species from the same genera.
Isolation and characterization of microsatellite loci in Sassafras randaiense (Lauraceae)
Authors: Chung Kuo‐Fang , Lin Ting‐Ting , Tsai Yung‐Shin , Lin Shu‐Tzong , Peng Ching‐I 
Published: October 2011

• Premise of the study: Microsatellite loci were developed in Sassafras randaiense, an endemic tree species in Taiwan, to investigate the conservation genetics of this invaluable plant that is at risk for continuing population decline.• Methods and Results: Using a magnetic bead enrichment method, 27 primer pairs amplifying di‐, tri, and tetranucleotide repeats were developed. Across the populations tested, 16 primer sets showed polymorphism, with an average of 4.06 alleles per polymorphic locus. Twenty of the 27 developed primer sets were also successfully amplified in its congener S. tzumu from China.• Conclusions: The new primer sets described here are a powerful tool for investigating the spatial patterns of genetic diversity and for designing effective management strategies for this invaluable plant.
Artinian and Non-Artinian Local Cohomology Modules
Authors: Dibaei Mohammad T. , Vahidi Alireza 
Published: October 2011

AbstractLet M be a finite module over a commutative noetherian ring R. For ideals a and b of R, the relations between cohomological dimensions of M with respect to a, b, a ⋂ b and a + b are studied. When R is local, it is shown that M is generalized Cohen–Macaulay if there exists an ideal a such that all local cohomology modules of M with respect to a have finite lengths. Also, when r is an integer such that 0 ≤ r < dimR(M), any maximal element q of the non-empty set of ideals ﹛a : (M) is not artinian for some i, i ≥ r} is a prime ideal, and all Bass numbers of (M) are finite for all i ≥ r.
The False Security of Closed XML Systems
Authors: Beck Jeff 
Published: October 2011

Creating and using XML documents in a closes system gives a false sense of “All’s Well”. A Closed XML system is one where a single party creates and uses the XML documents. Certainly this happens all of the time. We all create little XML documents with one-off throw-away models for one task or another that only we use. These documents will not be the focus here. When documents are created in a closed XML workflow and sent to another entity - such as an archive - for reuse, publishers can quickly learn that the content they have been accumulating is not useful for anything outside of their system and may not be useful if their own systems are upgraded or changed.
The checks and procedures that must be put in place to support XML interchange between entities should be applied within closed XML systems to keep the content usable and useful.