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Playing for half the deck: the molecular biology of meiosis
2002
Nature Cell Biology
Preserved Fulltext
Figure 2 2 Directionality of the meiotic process -D. melanogaster versus S. cerevisiae. a, In D. melanogaster, synapsis of homologues is required for exchange to occur. b, Conversely, in S. cerevisiae, ...
doi:10.1038/ncb-nm-fertilitys50
pmid:12479615
fatcat:vfwpqsgspvbfvcroztni5tgpie
Host-Pathogen O-Methyltransferase Similarity and Its Specific Presence in Highly Virulent Strains of Francisella tularensis Suggests Molecular Mimicry
2011
PLoS ONE
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In Mycobacterium avium 104, methyltransferase D mediates the methylation of highly antigenic glycopeptidolipids (GPLs) found densely distributed on the cell surface [36] . ...
Combined p-values for the motif profiles are shown next to each sequence. doi:10.1371/journal.pone.0020295.g005
Figure 6 . 6 Motif conservation profiles and polymorphic sites map proximal to a 3-D region ...
doi:10.1371/journal.pone.0020295
pmid:21637805
pmcid:PMC3102702
fatcat:y2ro5iz2u5ckpbk4zksvwipl2q
The Evolutionary History of Amino Acid Variations Mediating Increased Resistance of S. aureus Identifies Reversion Mutations in Metabolic Regulators
2013
PLoS ONE
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D
G
D
benign
0.439
benign
0.235
Tolerated
1.000
Neutral
0.235
purD
389
A
A
V
A
benign
Not Scored
benign
Not Scored
Tolerated
1.000
0
0.000
A9635
Vancomycin ...
The accuracy statistics of three methods in predicting StaphRAMs (A-C) is compared to the known accuracy of the same methods for predicting Human DAMs [21] (D) Maximum likelihood estimation of a binormal ...
doi:10.1371/journal.pone.0056466
pmid:23424663
pmcid:PMC3570469
fatcat:sjxjaeincfemxocipoa6fxvaka
IL-33 facilitates oncogene-induced cholangiocarcinoma in mice by an interleukin-6-sensitive mechanism
2015
Hepatology
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Furthermore, immunohistochemistry and immunofluorescence also demonstrated abundant ST2 expression in murine tumors (Fig. 5C,D) . ...
(D) Immunofluorescence was used to detect ST2 in murine CCA cells (CK19-positive) compared to cancer-associated fibroblasts (a-SMApositive) (left panel). ...
doi:10.1002/hep.27687
pmid:25580681
pmcid:PMC4406813
fatcat:x7jwyhecireuvcufm7svvdhwbq
When Outgroups Fail; Phylogenomics of Rooting the Emerging Pathogen, Coxiella burnetii
2013
Systematic Biology
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C G*A* Q321 A A C A T G C A C G G T C C G T A T T A C G G A C T C C T T C G A G C A G G G A G C T T D G D G A D D D D D G T C T A A A G C G A A' RSA 493 G G T A C*G*T* C C*G G T C T G T A T C G C G A A ...
D D D G C A A A A A A A A Q212 A* A* T* A* C G T A C T* G*D C T A C C G C G T A A G T C T T C C T C G A C A A A A G G T T C G*T* A*G*G G C A A A A G C G*A* Dugway A A C A C G T A C G G C C T A C C G C ...
doi:10.1093/sysbio/syt038
pmid:23736103
pmcid:PMC3739886
fatcat:cjyz6kyvczgthngxhkdciz7mnm
Phylogeography of Francisella tularensis subspecies holarctica from the country of Georgia
2011
BMC Microbiology
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Department of Homeland Security S&T CB Division Bioforensics R&D Program. ...
Table 1 1 Melt-MAMA primers targeting informative canSNPs SNP
SCHU
S4
position
Genome
SNP state
(D/A) a
Melt
MAMA
primer c
Melt-MAMA primer sequences d
Primer
conc. ...
c D: Derived; A: Ancestral; C: Common Primer
d Primer tails and antepenultimate mismatch bases are in lower case
Table 2 2 Francisella tularensis subsp. holarctica isolates from the country of Georgia ...
doi:10.1186/1471-2180-11-139
pmid:21682874
pmcid:PMC3224097
fatcat:sybi6ltlu5axdh6v3hifmgff34
Whole Genome Analyses of a Well-Differentiated Liposarcoma Reveals Novel SYT1 and DDR2 Rearrangements
2014
PLoS ONE
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Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has
doi:10.1371/journal.pone.0087113
pmid:24505276
pmcid:PMC3914808
fatcat:2ry7r5koerc67nkzenjgfix6cm
more »
... y been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.
Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies
2009
PLoS Pathogens
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genes (and psuedogenes) that encode components of the Twin Arginine Translocation (TAT), and secretion systems of Type I (T1SS), Type II (T2SS), Type V (T5SS), and VI (T6SS) ( Tables 4-6 and Table S1c ,d, ...
regulator of transcription (sspA)
FTT0557
hypothetical protein ahpC/TSA family
FTT0623
trigger factor (TF) protein (peptidyl-prolyl cis/trans isomerase)
FTT0628
peptidyl-prolyl cis-trans isomerase D ...
doi:10.1371/journal.ppat.1000459
pmid:19478886
pmcid:PMC2682660
fatcat:76urr2746zbcte2ht2bugtfst4
Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers
2016
Scientific Reports
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DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/ refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using
doi:10.1038/s41598-016-0021-4
pmid:28003660
pmcid:PMC5431338
fatcat:myuvizoldjacfgcagctgt7lbey
more »
... LIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1-3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIeNTIfIC REPORts | 6: 25 | profiling. Eighteen of 66 treated patients (27%) were found to have progression-free survival (PFS) ≥1.3 times longer on the molecular profiling directed approach compared to their most recent empiric therapy (PFS ratio), allowing for rejection of the null hypothesis of <15% having PFS ratio ≥1.3. In a similar effort focused on patients treated on Phase I trials, Tsimberidou and colleagues assessed microdissected paraffin embedded tissue for somatic hot-spot exonal mutations in 10 genes (PIK3CA, BRAF, NRAS, KRAS, EGFR, KIT, GNAQ, MET, TP53 and RET), IHC for PTEN and FISH for ALK translocations in 1,144 patients 7 . They found that 460 (40.2%) of these patients had at least one genomic aberration. Notably, a higher response rate (27% vs. 5%; P < 0.0001), time-to-treatment failure (median 5.2 vs. 2.2 months; P < 0.0001) and longer survival (median 13.4 vs. 9.0 months; P = 0.017) were observed in patients who had matched therapy compared to those patients who had empiric therapy. While the scope of molecular profiling performed in these studies was limited compared to current NGS enabled approaches, they provide a contextual platform upon which clinical efforts utilising NGS could be implemented. NGS based approaches assaying a panel of genes 4 or a panel of genes in conjunction with array comparative genomic hybridisation (aCGH) 8 , provided further impetus towards more ambitious, comprehensive genomic characterisation in the clinical setting. More recently, a retrospective study by Jones and colleagues comparing whole exome sequencing to NGS panel based approaches, highlighted the high false positive rate and absence of germline analysis associated with NGS panels as major limitations 9 . Several other recent studies have further demonstrated the necessity of including germline analysis when evaluating somatic mutations 10-13 . Exploratory evaluations of whole exome, genome and transcriptome sequencing have demonstrated the technical feasibility of the approach. However, these efforts were limited (Weiss and colleagues [n = 9] 3 and Roychowdhury and colleagues [n = 4] 5 ) and identified numerous barriers that should be evaluated in future studies. These barriers include the ability to execute the workflow consistently in a Clinical Laboratory Improvement Amendments (CLIA) 14 environment and challenges in acquisition of sufficient, high-quality, NGS suitable tissue from prospectively collected samples. Furthermore, ethical, legal, and social implications (ELSI) are significant as these encompass the communication of incidental (unsolicited) findings from germline analysis, data custody and data privacy in the event of death prior to result availability. In addition, the delivery of results to treating physicians in a timeframe that is compatible with the opportunity to treat patients experiencing clinical decline while awaiting results and access to genome analysis guided therapeutics through on/off-label use of drugs or clinical studies, present very real barriers to implementation of comprehensive NGS technologies in the clinic. In response to these observed challenges, a study was designed to evaluate the effectiveness of implementation of comprehensive NGS technologies in a clinical setting. The study objectives were threefold. First, the study sought to estimate the time to completion of integrated whole exome/long insert whole genome/transcriptome sequencing. Second, the objective was to estimate time to reporting of results of therapeutically relevant drug targets derived from integrated whole exome/long-insert whole genome/whole transcriptome sequencing along with CLIA validation. Finally, the study sought to determine mechanisms of drug access.
The clinical significance of cereblon expression in multiple myeloma
2014
Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis
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a)-(d) CRBN expression in MM and its precursors. ...
This increase is not only explained by copy number dependency of CRBN expression (shown in D).
Fig. 3 . 3 Fig. 3.
Fig. 4 . 4 CRBN expression correlates with PFS (A+C) and OS (B+D). ...
doi:10.1016/j.leukres.2013.08.015
pmid:24129344
pmcid:PMC3905958
fatcat:ozz6nm2ipzatlpopwmznm7dizi
Targeted sequencing using a 47 gene multiple myeloma mutation panel (M3P) in -17p high risk disease
2014
British Journal of Haematology
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We constructed a multiple myeloma (MM)-specific gene panel for targeted sequencing and investigated 72 untreated high-risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high-risk MM. Additionally, our
doi:10.1111/bjh.13171
pmid:25302557
pmcid:PMC4314325
fatcat:vln4emku3vcrnihcs4zhml5vfa
more »
... k demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM.
A Multidisciplinary Biospecimen Bank of Renal Cell Carcinomas Compatible with Discovery Platforms at Mayo Clinic, Scottsdale, Arizona
2015
PLoS ONE
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D, Gene-body coverage by H3K36me3-binding sites. ...
doi:10.1371/journal.pone.0132831
pmid:26181416
pmcid:PMC4504486
fatcat:yujszsknnzbqlnpmqdnbywqxs4
Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma
2014
PLoS Genetics
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D) Tumor stained with pEGFR showing membranous positivity (solid arrows) with negative background lymphocytes (empty arrows). ...
Summaries by individual patients are shown as follows: A) Patient 1, B) Patient 2, C) Patient 3, D) Patient 4, E) Patient 5, and F) Patient 6. ...
doi:10.1371/journal.pgen.1004135
pmid:24550739
pmcid:PMC3923676
fatcat:gtjn2vzmwngmfguyyqurcxqbvy
Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis
2011
PLoS Genetics
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Our analysis indicated that the Paracoccidioides genome encodes for the catabolic pathways necessary to break down plant cell wall derived monosaccharides D-glucose, D-xylose, and D-mannose, and D-galactose ...
U. reesii grew well on monosaccharides Dglucose, D-mannose, and D-xylose in at least two of the three replicates. ...
doi:10.1371/journal.pgen.1002345
pmid:22046142
pmcid:PMC3203195
fatcat:gdxwoeboa5bodhpx3hmbwuscyu
Page 898 of Guernsey Breeders' Journal Vol. 98, Issue 6
[page]
1956
Guernsey Breeders' Journal
Preserved Fulltext
The Internet Archive has digitized a microfilm copy of this work. It may be possible to borrow a copy for reading.
Bom October 23, 1950
Mia liiiiii Mia Hin-'a Ditiii
< Itl.ltSI'HINO'H II. ...
D. No. 1 Pennsylvania
Band's Kree 11923
.lOSKBH KKTHKROLK Manager
Tel. Orwigsburg—Empire 6-5872
Guernsey Breeders' Journal
\ ...
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