gebhart/patrepeval huggingface dataset:
A Multifactorial Likelihood Model for MMR Gene Variant Classification Incorporating Probabilities Based on Sequence Bioinformatics and Tumor Characteristics: A Report from the Colon Cancer Family Registry (2012)

Mismatch repair (MMR) gene sequence variants of uncertain clinical significance are often identified in suspected Lynch syndrome families, and this constitutes a challenge for both researchers and clinicians. Multifactorial likelihood model approaches provide a quantitative measure of MMR variant pathogenicity, but first require input of likelihood ratios (LRs) for different MMR variation-associated characteristics from appropriate, well-characterized reference datasets. Microsatellite instability (MSI) and somatic BRAF tumor data for unselected colorectal cancer probands of known pathogenic variant status were used to derive LRs for tumor characteristics using the Colon Cancer Family Registry (CFR) resource. These tumor LRs were combined with variant segregation within families, and estimates of prior probability of pathogenicity based on sequence conservation and position, to analyze 44 unclassified variants identified initially in Australasian Colon CFR families. In addition, in vitro splicing analyses were conducted on the subset of variants based on bioinformatic splicing predictions. The LR in favor of pathogenicity was estimated to be ~12-fold for a colorectal tumor with a BRAF mutation-negative MSI-H phenotype. For 31 of the 44 variants, the posterior probabilities of pathogenicity were such that altered clinical management would be indicated. Our findings provide a working multifactorial likelihood model for classification that carefully considers mode of ascertainment for gene testing.
Wnt6 controls amniote neural crest induction through the non‐canonical signaling pathway (2007)

The neural crest is a multipotent embryonic cell population that arises from neural ectoderm and forms derivatives essential for vertebrate function. Neural crest induction requires an ectodermal signal, thought to be a Wnt ligand, but the identity of the Wnt that performs this function in amniotes is unknown. Here, we demonstrate that Wnt6, derived from the ectoderm, is necessary for chick neural crest induction. Crucially, we also show that Wnt6 acts through the non-canonical pathway and not the beta-catenin-dependant pathway. Surprisingly, we found that canonical Wnt signaling inhibited neural crest production in the chick embryo. In light of studies in anamniotes demonstrating that canonical Wnt signaling induces neural crest, these results indicate a significant and novel change in the mechanism of neural crest induction during vertebrate evolution. These data also highlight a key role for noncanonical Wnt signaling in cell type specification from a stem population during development.
ACQUIRED RESISTANCE TO ANTIBIOTICS (1947)

Editorial1 August 1947ACQUIRED RESISTANCE TO ANTIBIOTICSP. W. C.P. W. C.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-27-2-317 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt has long been recognized that microörganisms may acquire a marked degree of resistance to a drug as a result of exposure to sublethal concentrations, although originally they were highly sensitive to its action. This phenomenon was first brought to general notice by Ehrlich nearly half a century ago in his studies of the action of arsenicals in spirochetal and trypanosomal infections. He applied the term drug-fast to such resistant strains.In the more recent past many similar observations have been made with respect to the sulfonamides. Many highly susceptible species of organisms, such as the pneumococcus, the streptococcus and...1 ALEXANDERLEIDY HEG: Mode of action of streptomycin on Type b H. influenzae. I. Origin of resistant organisms, Jr. Exper. Med., 1947, lxxxv, 329-337. CrossrefGoogle Scholar2 MILLERBONNHOFF CPM: Development of streptomycin-resistant variants of meningococcus, Science, 1947, cv, 620. CrossrefGoogle Scholar3 ALEXANDERLEIDY HEG: Mode of action of streptomycin on Type b Hemophilus influenzae. II. Nature of resistant variants, Jr. Exper. Med., 1947, lxxxv, 607-621. CrossrefGoogle Scholar4 DEMEREC M: Production of staphylococcus strains resistant to various concentrations of pencillin, Proc. Nat. Acad. Sci., 1945, xxxi, 16. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBACTERIAL VERSATILITYH. J. L. M. 1 August 1947Volume 27, Issue 2Page: 317-319KeywordsAntibioticsAttentionDrugsEhrlichiosisPneumococcusStreptococcusSulfonamide ePublished: 1 December 2008 Issue Published: 1 August 1947 PDF downloadLoading ...
On infostation density of vehicular networks (2010)

Vehicle-to-Vehicle and Vehicle-to-Roadside communications are going to become an indispensable part of the modern day automotive experience. For people on the move, vehicular networks can provide critical network connectivity and access to real-time information. Infestations play a vital role in the
A Comparison of Alternative Techniques for Portfolio Optimization: A Case Study by the Pikes Peak Area Council of Governments (2016)

The evaluation and prioritization of transportation investments at the portfolio level presents a complex decision-making problem for planning organizations. Historically, investment decisions were treated as stand-alone problems. Improvement needs and solutions were identified using only engineering-based criteria, with portfolio optimization accomplished by ranking projects in order of criteria satisfaction and then prioritizing funding allocation based on rank. Increasing awareness of the complex interdependencies among transportation, land-use, social, economic and ecological systems has fostered implementation investment prioritization approaches that incorporate increasingly more complex goals and metrics. The simplest among newer decision models is the Weighted Score Method (WSM). More rigorous methods, including the Technique for Ordered Preference by Similarity to Ideal Solution (TOPSIS) and Logic Scoring of Preference (LSP), support prioritization driven by asset performance and financial return. A downside of more complex methodologies is a lack of transparency that can foster distrust in results. To build confidence in project prioritization equity associated with more rigorous methodologies, the Colorado Springs Metropolitan Planning Organization (MPO) engaged collaborating partners in a process utilizing three alternative project scoring and prioritization methodologies: 1) WSM; 2) TOPSIS; and 3) LSP. This paper examines the result produced by each methodology, the suitability of each for the optimization of transportation investment priorities, and acceptance of results. The application of each differing approach is contrasted alternative approaches. Functionality, advantages, and disadvantages of each approach are discussed, and potential enhancements are identified. The effectiveness of the multi-technique scoring exercise in building project prioritization consensus is also examined.
Measuring intramuscular fat in beef with ultrasonic frequency analysis (1994)

Frequency analysis of Fourier spectra from ultrasonic signals was used for predicting intramuscular fat content of beef tissue. The most significant parameter in the frequency domain for predicting intramuscular fat concentration in beef was the number of local maxima. It represents the discontinuity of the Fourier spectrum caused by inhomogeneous fat concentrations in the longissimus muscle, which had the correlation coefficient .89 (P < .05) when a 2.25-MHz shear probe was used. The optimum frequency for predicting the amount of intramuscular fat content in the longissimus muscle was found to be 1.92 MHz. A multivariate regression model was developed using parameters in the frequency domain as follows: percentage of fat concentration = 1.790 - 2.373x (lower frequency) + .049x (bandwidth) + 1.178x (local maxima) (R2 = .82). Validation demonstrated that the multivariate model in the frequency domain was capable of predicting intramuscular fat concentration with an average of 1.17 percentage of fat error (P < .05). The multivariate model was most appropriate for predicting intramuscular fat below 4%. The mean accuracy of the model in the frequency domain was approximately 79%.
Identification of Poultry Meat‐Derived Fatty Acids Functioning as Quorum Sensing Signal Inhibitors to Autoinducer‐2 (AI‐2) (2007)

Autoinducer-2 (AI-2) is a compound that plays a key role in bacterial cell-to-cell communication (quorum sensing). Previous research has shown certain food matrices inhibit this signaling compound. Using the reporter strain, Vibrio harveyi BB170, quorum-sensing inhibitors contained in poultry meat wash (PMW) samples were characterized by molecular weight and hydrophobic properties using liquid chromatography systems. Most fractions that demonstrated AI-2 inhibition were 13.7 kDa or less, and had hydrophobic properties. Hexane was used to extract inhibitory compounds from a PMW preparation and the extract was further separated by gas chromatography (GC). Several fatty acids were identified and quantified. Linoleic acid, oleic acid, palmitic acid, and stearic acid were each tested for inhibition at 0.1, 1, and 10 mM concentrations. All samples expressed AI-2 inhibition (ranging from approximately 25% to 99%). Fatty acids, combined in concentrations equivalent to those determined by GC analysis, expressed inhibition at 59.5%, but higher combined concentrations (10- and 100-fold) had inhibition at 84.4% and 69.5%, respectively. The combined fatty acids (100-fold) did not demonstrate a substantial decrease in colony plate counts, despite presenting high AI-2 inhibition. These fatty acids, through modulating quorum sensing by inhibition, may offer a unique means to control foodborne pathogens and reduce microbial spoilage.
The Ammonia Spectrum and Line Shapes Near 1.25-cm Wave-Length (1946)

The ammonia "inversion" lines near 1.25-cm wave-length are resolved, their widths being decreased at low pressures to 200 kilocycles. Line shapes, intensities, and frequencies are measured and correlated with theory. Calculated intensities and Lorentz-type broadening theory fit experimental results if frequency of collision is fifteen times greater than that measured by viscosity methods. Splitting due to rotation is in fair agreement with a recalculation of theoretical values. A saturation effect is observed with increase of power absorbed per molecule and an interpretation made.
High Temperature Deformation of a Yttria-Stabilized Tetragonal Zirconia (2001)

The creep behavior of a high-purity tetragonal zirconia polycrystal containing 3 mol% yttria (3Y-TZP) is characterized with a stress exponent of n∼2.7 and a grain size exponent of p∼2.0-3.0 in a high stress region, and with n∼1.3 and p∼2.0 in a low stress region. These regions are connected with a transition region with n≥5, and accordingly the creep stress-strain rate relationship as a whole exhibits a sigmoidal feature. The apparent activation energy in the high and the low stress regions is the same, 580 kJ/mol, which corresponds to a value reported for lattice diffusion of cations. In the high stress region, evidence of intragranular dislocations revealed by TEM suggests that the motion of intragranular dislocations would contribute to the accommodation process of grain boundary sliding. In the low stress region where such dislocations were not observed, the combination of n∼1.3 and p∼2.0 suggests an intervention of lattice diffusion creep.
immuneML: an ecosystem for machine learning analysis of adaptive immune receptor repertoires (2021)

Abstract Adaptive immune receptor repertoires (AIRR) are key targets for biomedical research as they record past and ongoing adaptive immune responses. The capacity of machine learning (ML) to identify complex discriminative sequence patterns renders it an ideal approach for AIRR-based diagnostic and therapeutic discovery. To date, widespread adoption of AIRR ML has been inhibited by a lack of reproducibility, transparency, and interoperability. immuneML ( immuneml.uio.no ) addresses these concerns by implementing each step of the AIRR ML process in an extensible, open-source software ecosystem that is based on fully specified and shareable workflows. To facilitate widespread user adoption, immuneML is available as a command-line tool and through an intuitive Galaxy web interface, and extensive documentation of workflows is provided. We demonstrate the broad applicability of immuneML by (i) reproducing a large-scale study on immune state prediction, (ii) developing, integrating, and applying a novel method for antigen specificity prediction, and (iii) showcasing streamlined interpretability-focused benchmarking of AIRR ML.
El lado salvaje de Europa (2010)

Algunos de los mejores fotografos europeos captan la fauna y los paisajes naturales del Viejo Continente.
EMT: Present and future in clinical oncology (2017)

Epithelial/mesenchymal transition (EMT) has emerged as a key regulator of metastasis by facilitating tumor cell invasion and dissemination to distant organs. Recent evidences support that the reverse mesenchymal/epithelial transition (MET) is required for metastatic outgrowth; moreover, the existence of hybrid epithelial/mesenchymal (E/M) phenotypes is increasingly being reported in different tumor contexts. The accumulated data strongly support that plasticity between epithelial and mesenchymal states underlies the dissemination and metastatic potential of carcinoma cells. However, the translation into the clinics of EMT and epithelial plasticity processes presents enormous challenges and still remains a controversial issue. In this review, we will evaluate current evidences for translational applicability of EMT and depict an overview of the most recent EMT in vivo models, EMT marker analyses in human samples as well as potential EMT therapeutic approaches and ongoing clinical trials. We foresee that standardized analyses of EMT markers in solid and liquid tumor biopsies in addition to innovative tools targeting the E/M states will become promising strategies for future translation to the clinical setting.
Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters. (1989)

Cotransport proteins are responsible for the active accumulation of organic substrates in cells. Na+ gradients provide the driving force for uptake of most substrates into eukaryotes and for a few substrates in some prokaryotes. We report here the cloning and sequencing of the human intestinal Na+/glucose cotransporter (SGLT1) and compare its structure with other cloned transporters. At the DNA level and the predicted amino acid and secondary structure levels, close homology is evident between the human and rabbit intestinal Na+/glucose cotransporters, and a significant homology is found between these and the Escherichia coli Na+/proline cotransporter (putP). No homology is detectible with other known proteins. We infer from these results that the mammalian Na+/glucose and prokaryote Na+/proline cotransporters share a common ancestral gene.
Relation of Plasmids to Virulence and Other Properties of Salmonellae from Avian Sources (1987)

A collection of 185 isolates of 34 serovars of Salmonella from avian sources was examined for plasmids, drug resistance, biochemical properties, serum resistance, and virulence. No serovars other than S. enteritidis, S. typhimurium, and S. heidelberg showed evidence of serovar-associated plasmids. All S. enteritidis isolates carried a single plasmid of 36 Mdal and were resistant to guinea pig serum; one strain that was tested was virulent. Of 27 isolates of S. typhimurium, 11 possessed a 60-Mdal plasmid and 17 harbored a 2.3-Mdal plasmid. Among isolates of S. heidelberg, 21 of 24 carried a 2.2-Mdal plasmid. The only biochemical property that varied was fermentation of inositol, which tended to be related to serovar. Of 172 isolates, 54 were resistant to at least one drug. Multiple drug resistance was usually associated with R plasmids, and transmissible plasmids that encoded resistance to chloramphenicol and gentamicin were demonstrated. Of 117 isolates tested, 43 were resistant to guinea pig serum. Resistance appeared to be a characteristic of isolates rather than serovar and could not be related to plasmids. Twenty-five isolates highly resistant to guinea pig serum were all susceptible to the bactericidal action of chicken serum. In tests for virulence using intraperitoneally (i.p.) and orally inoculated Balb/c mice and day-old chicks, only i.p.-inoculated chicks proved useful in demonstrating large differences among isolates: LD50's ranged from 10(0) to 10(8).
Scoparone interferes with STAT3-induced proliferation of vascular smooth muscle cells (2015)

Scoparone, which is a major constituent of Artemisia capillaries, has been identified as an anticoagulant, hypolipidemic, vasorelaxant, anti-oxidant and anti-inflammatory drug, and it is used for the traditional treatment of neonatal jaundice. Therefore, we hypothesized that scoparone could suppress the proliferation of VSMCs by interfering with STAT3 signaling. We found that the proliferation of these cells was significantly attenuated by scoparone in a dose-dependent manner. Scoparone markedly reduced the serum-stimulated accumulation of cells in the S phase and concomitantly increased the proportion of cells in the G0/G1 phase, which was consistent with the reduced expression of cyclin D1, phosphorylated Rb and survivin in the VSMCs. Cell adhesion markers, such as MCP-1 and ICAM-1, were significantly reduced by scoparone. Interestingly, this compound attenuated the increase in cyclin D promoter activity by inhibiting the activities of both the WT and active forms of STAT3. Similarly, the expression of a cell proliferation marker induced by PDGF was decreased by scoparone with no change in the phosphorylation of JAK2 or Src. On the basis of the immunofluorescence staining results, STAT3 proteins phosphorylated by PDGF were predominantly localized to the nucleus and were markedly reduced in the scoparone-treated cells. In summary, scoparone blocks the accumulation of STAT3 transported from the cytosol to the nucleus, leading to the suppression of VSMC proliferation through G1 phase arrest and the inhibition of Rb phosphorylation. This activity occurs independent of the form of STAT3 and upstream of kinases, such as Jak and Src, which are correlated with abnormal vascular remodeling due to the presence of an excess of growth factors following vascular injury. These data provide convincing evidence that scoparone may be a new preventative agent for the treatment of cardiovascular diseases.
Measurement of Serum Ionic Calcium Using a Specific Ion Electrode (1968)

Journal Article Measurement of Serum Ionic Calcium Using a Specific Ion Electrode Get access Dorothy E. Arnold, B.A., M.T. (ASCP), Dorothy E. Arnold, B.A., M.T. (ASCP) United States Air Force School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks Air Force Base, Texas 78285 Search for other works by this author on: Oxford Academic Google Scholar Marion J. Stansell, CAPT., USAF, BSC, Marion J. Stansell, CAPT., USAF, BSC United States Air Force School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks Air Force Base, Texas 78285 Search for other works by this author on: Oxford Academic Google Scholar Harry H. Malvin, Major, USAF, MC Harry H. Malvin, Major, USAF, MC United States Air Force School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks Air Force Base, Texas 78285 Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 49, Issue 5, 1 May 1968, Pages 627–634, https://doi.org/10.1093/ajcp/49.5.627 Published: 01 May 1968 Article history Received: 22 May 1967 Published: 01 May 1968
A Series of Substituted Propylene Carbonate (PC) – An Investigation of Graphite Exfoliation (2013)

Abstract not Available.
Allogeneic and Autologous Telomerase-Positive Stem Cells as a Potential Treatment for Systemic Lupus Erythematosus (2020)

Systemic lupus erythematosus (SLE) is a chronic incurable and potentially fatal autoimmune disease. SLE manifests itself with the production of autoantibodies to partially digested nuclear components, cells, and non-cellular material. With any type of tissue insult, there is a release of material from damaged tissues which initiates a cascade of events that perpetuate a lupus flare/crisis, resulting in replacement of functional tissue with non-functional scar tissue in all organs of the body. Current pharmacological interventions use immunosuppressive therapy, cytotoxic agents, and/or biologics to halt the progression of SLE. Studies are ongoing to prove the utility of stem cells to cure people with chronic diseases. Myeloablation followed with HLA-matched hematopoietic stem cells demonstrate its ability to halt the progression of SLE. Mesenchymal stem cells demonstrate an immunomodulatory effect on the immune system, slowing the progression of SLE. Neither stem cell treatment has shown an increase in systemic organ functioning. We hypothesize that telomerase-positive stem cells would halt progression of disease and increase systemic organ functioning. A 61-year-old male was diagnosed as two-week terminal stage-IV SLE, with systemic organs functioning at or below 25%. He was treated with multiple autologous and allogeneic telomerasepositive stem cell transplants. He is still alive after 9+ years and his organs are functioning at or near 70%.
Ground state Gamow-Teller strength in sup 64 Ni(n,p) sup 64 Co (1991)

An important process occurring in presupernova stars is e{sup {minus}} capture on free protons and nuclei. As e{sup {minus}} capture and the charge exchange reaction (n,p) between same initial and final states are both T{sub 0} {yields} T{sub 0} + 1 transitions involving the same nuclear matrix element, the (n,p) reaction can be used to provide the input required to calculate e{sup {minus}} capture rates. Specifically, the e{sup {minus}} capture rate {lambda}{sup if} for a nucleus going from an initial state i to a final state f is proportional to the Gamow-Teller strength B{sup if}. Once B{sup if} for a particular transition is known, the corresponding e{sup {minus}} capture rate {lambda}{sup if} for that transition can be calculated. The unit cross section {cflx {sigma}}{sub GT}(E,A) relates B{sup if} to the zero degree differential cross section extrapolated to q = 0 for (n,p) or (p,n) reactions: {sigma}(q = 0) = {cflx {sigma}}(E,A)B{sup if}. As {cflx {sigma}}(E,A) has been seen to have a smooth A dependence, measurements of zero degree (n,p) cross sections for (fp) shell nuclei can be used to obtain B{sup if}, and thus {lambda}{sup if}, once a value for {cflx {sigma}}(E,A) in this mass region is known. The data presented here allow a value for {cflx {sigma}}{sub GT} in the (fp) shell to be calculated from the Gamow-Teller strength for the {beta}{sup {minus}} decay {sup 64}Co {yields} {sup 64}Ni + e{sup {minus}} + {bar {nu}}{sub e}. Since {sup 64}Co {beta}{sup {minus}} decay and the reaction {sup 64}Ni(n,p) {sup 64}Co have opposite initial and final states, detailed balance can be used to relate the Gamow-Teller strengths for the two processes: B{sup np} = 0.6228{sub {minus}.0369}{sup +.0328}. It is this value of B{sup np} together with the differential cross section measurements presented here for the reaction {sup 64}Ni(n,p) {sup 64}Co that allow {cflx {sigma}} to be calculated and thus a calibration point in the (fp) shell is established.