tbuckley/cabot-search huggingface dataset:
SPIn: Model Selection for Phylogenetic Mixtures via Linear Invariants
Authors: A. M. Kedzierska, M. Drton, R. Guigo, M. Casanellas
Journal: Molecular Biology and Evolution (2011)

In phylogenetic inference, an evolutionary model describes the substitution processes along each edge of a phylogenetic tree. Misspecification of the model has important implications for the analysis of phylogenetic data. Conventionally, however, the selection of a suitable evolutionary model is based on heuristics or relies on the choice of an approximate input tree. We introduce a method for model Selection in Phylogenetics based on linear INvariants (SPIn), which uses recent insights on linear invariants to characterize a model of nucleotide evolution for phylogenetic mixtures on any number of components. Linear invariants are constraints among the joint probabilities of the bases in the operational taxonomic units that hold irrespective of the tree topologies appearing in the mixtures. SPIn therefore requires no input tree and is designed to deal with nonhomogeneous phylogenetic data consisting of multiple sequence alignments showing different patterns of evolution, for example, concatenated genes, exons, and/or introns. Here, we report on the results of the proposed method evaluated on multiple sequence alignments simulated under a variety of single-tree and mixture settings for both continuous- and discrete-time models. In the simulations, SPIn successfully recovers the underlying evolutionary model and is shown to perform better than existing approaches.
Effect of contact avoidance or treatment with oral prednisolone on bronchoalveolar lavage surfactant protein A levels in subjects with farmer's lung.
Authors: Y. Cormier, E. Israel-Assayag, M. Desmeules, O. Lesur
Journal: Thorax (1996)

Surfactant protein A (SP-A) acts as an immune system modulator in the lungs and may therefore be involved in the pathogenesis of hypersensitivity pneumonitis.The levels of SP-A in bronchoalveolar lavage (BAL) fluid were measured in 20 subjects with acute farmer's lung, 16 asymptomatic dairy farmers, and 14 normal controls. Eight patients had a second evaluation after one month of treatment by either contact avoidance (n = 3) or oral prednisolone (20 or 25 mg/day, n = 5). Chest radiographs and lung function measurements were also obtained in all farmers, twice in those re-evaluated after treatment.Patients with acute farmer's lung had significantly higher levels of SP-A than asymptomatic farmers and normal controls (p = 0.005) with mean (SE) values of 1.43 (0.29) micrograms/ml, 0.62 (0.09) microgram/ml, and 0.68 (0.11) microgram/ml, respectively. In eight subjects tested after one month of treatment the level of SP-A was unchanged although all were clinically improved. No correlations were seen between levels of SP-A in BAL fluid and numbers of BAL cells, lung function measurements, or chest radiographic scores.Although the level of SP-A is increased in the BAL fluid of patients with acute farmer's lung, it is not correlated with clinical abnormalities of this disease.
Heart rate-based lactate minimum test: a reproducible method
Authors: M Strupler, G Mueller, C Perret
Journal: British Journal of Sports Medicine (2008)

To find the individual intensity for aerobic endurance training, the lactate minimum test (LMT) seems to be a promising method. LMTs described in the literature consist of speed or work rate-based protocols, but for training prescription in daily practice mostly heart rate is used. The aim of the present study was to investigate the reproducibility of a new heart rate-based LMT protocol.20 subjects each underwent four LMTs on a cycle ergometer. The LMT consisted of a first part (Conconi test) to induce lactate accumulation and a second part (incremental protocol) with stages of 5 min starting beyond the aerobic threshold. During these stages work rate was adjusted to reach predetermined heart rates, which were calculated for every single test from heart rate (HR) at rest and maximum HR. Lactate was measured after each stage to define the lactate minimum (LM) and the corresponding HR.Institute of Sports Medicine.20 healthy and endurance-trained individuals (13 men, seven women).Reproducibility of heart rate at LM.The reproducibility of heart rate at LM was high (coefficient of variation (CV) = 2.1%). The reproducibility of work rate at LM was good (CV = 6.7%). CV for lactate concentrations at LM was 17.4%. High interindividual differences at LM were found in heart rate (range 149-178 beats/min) and lactate levels (range 1.2-6.8 mmol/l).The LMT using a heart rate-based protocol is a reproducible method of assessing HR at an exercise intensity where an equilibrium exists between blood lactate accumulation and elimination.
Phosrestin I undergoes the earliest light-induced phosphorylation by a calcium/calmodulin-dependent protein kinase in drosophila photoreceptors
Authors: Hiroyuki Matsumoto, Biji T. Kurien, Yuichiro Takagi, Esther S. Kahn, Tomoya Kinumi, Naoka Komori, Takuma Yamada, Fumio Hayashi, Kunio Isono, William L. Pak, Kenneth W. Jackson, Sara L. Tobin
Journal: Neuron (1994)
Effect of functional knee brace use on acceleration, agility, leg power and speed performance in healthy athletes
Authors: Neetu Rishiraj, Jack E Taunton, Robert Lloyd-Smith, William Regan, Brian Niven, Robert Woollard
Journal: British Journal of Sports Medicine (2011)

Objectives To investigate performance levels and accommodation period to functional knee brace (FKB) use in non-injured braced subjects while completing acceleration, agility, lower extremity power and speed tasks. Design A 2 (non-braced and braced conditions) × 5 (testing sessions) repeated-measures design. Methods 27 healthy male athletes were provided a custom fitted FKB. Each subject performed acceleration, agility, leg power and speed tests over 6 days; five non-braced testing sessions over 3 days followed by five braced testing sessions also over 3 days. Each subject performed two testing sessions (3.5 h per session) each day. Performance levels for each test were recorded during each non-braced and braced trial. Repeated measures analysis of variance, with a post hoc Tukey's test for any test found to be significant, were used to determine if accommodation to FKB was possible in healthy braced subjects. Results Initial performance levels were lower for braced than non-braced for all tests (acceleration p=0.106; agility p=0.520; leg power p=0.001 and speed p=0.001). However, after using the FKB for approximately 14.0 h, no significant performance differences were noted between the two testing conditions (acceleration non-braced, 0.53±0.04 s; braced, 0.53±0.04 s, p=0.163, agility non-braced, 9.80±0.74 s; braced, 9.80±0.85 s, p=0.151, lower extremity power non-braced, 58±7.4 cm; braced, 57±8.1 cm, p=0.163 and speed non-braced, 1.86±0.11 s; braced, 1.89±0.11 s, p=0.460). Conclusions An initial decrement in performance levels was recorded when a FKB is used during an alactic performance task. After 12.0–14.0 h of FKB use, performance measures were similar between the two testing conditions.
Protein Allergenicity Assessment of Foods Produced Through Agricultural Biotechnology
Authors: Steve L. Taylor
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Foods produced through agricultural biotechnology are reaching the consumer marketplace. These novel foods should be assessed for their safety, including their potential allergenicity. Agricultural biotechnology involves the introduction of novel proteins into the modified foods, and proteins can be allergenic. The potential allergenicity of the introduced proteins can be evaluated by focusing on the source of the gene, the homology of the newly introduced protein to known allergens, the reactivity of the novel protein with IgE antibodies from the serum of individuals with known allergies to the source of the transferred DNA or to materials that are broadly related to the source of the transferred DNA, the resistance of the novel protein to pepsin, and the immunoreactivity of the novel protein in appropriate animal models. Additional factors, such as the level of expression of the novel protein in the modified food and expression in the edible portion of the food, may also yield valuable insights. Applying such criteria provides a reasonable approach to determining whether or not the novel protein is likely to become an allergen.
Treatment outcome and factors associated with unfavourable treatment results in cases with multidrug-resistant tuberculosis in Bulgaria for the period 2009-2010
Authors: Vladimir Milanov, Mariya Zamfirova, Tonka Varleva, Elizabeta Bachiyska, Antoniya Koleva
Journal: European Respiratory Journal (2012)

A retrospective study of all patients with MDR-TB in Bulgaria who started treatment for the period September 2009-March 2010 was performed. Aim: To make treatment outcome analysis and to determine the factors associated with unfavourable treatment results in cases with MDR-TB. Materials and methods: Medical records, recording and reporting forms for the MDR-TB cases included in treatment and TB registries of the NRL-TB were examined. Results: A total of 50 MDR-TB patients with mean age 45.8 years started treatment during the period. The male to female ratio was 2.3:1. Nineteen patients (38%) were new, and the other 31 cases were previously treated: 12 relapses (24%), after failure – 8 (16%), after default – 10 (20%). The median duration of recorded disease before treatment was 3.1 years (range, 0-13). None of all the patients tested for HIV had a positive result. Eight cases were found with XDR-TB during the treatment: 4 in 2010, and 4 – in 2011. Treatment was given for 18-24 months, including at least 12 months after culture conversion. Twenty four months after beginning of treatment, 24 patients (48%) were cured, 19 patients (38%) died, and one patient (2%) interrupted treatment. The cases with XDR-TB had higher mortality rate than the other MDR-TB cases (75% vs. 30.9%). Conclusion: This study shows high mortality rate in MDR-TB cases during two years after treatment initiation. XDR-TB is the strongest predictor of poor treatment outcomes. Previous TB treatment, weight loss and positive smears for acid-fast bacilli at the start of treatment are the other important factors associated with unfavourable treatment results.
Serial Cardiac Magnetic Resonance Imaging of Injected Mesenchymal Stem Cells
Authors: Jonathan M. Hill, Alexander J. Dick, Venkatesh K. Raman, Richard B. Thompson, Zu-Xi Yu, K. Allison Hinds, Breno S.S. Pessanha, Michael A. Guttman, Timothy R. Varney, Bradley J. Martin, Cynthia E. Dunbar, Elliot R. McVeigh, Robert J. Lederman
Journal: Circulation (2003)

Delivery and tracking of endomyocardial stem cells are limited by the inability to image transplanted cells noninvasively in the beating heart. We hypothesized that mesenchymal stem cells (MSCs) could be labeled with a iron fluorophore particle (IFP) to provide MRI contrast in vivo to assess immediate and long-term localization.MSCs were isolated from swine. Short-term incubation of MSCs with IFP resulted in dose-dependent and efficient labeling. Labeled cells remained viable for multiple passages and retained in vitro proliferation and differentiation capacity. Labeled MSCs (10(4) to 10(6) cells/150 microL) were injected percutaneously into normal and freshly infarcted myocardium in swine. One, 3, and 1 animals underwent serial cardiac MRI (1.5T) for 4, 8, and 21 days, respectively. MRI contrast properties were measured both in vivo and in vitro for cells embedded in agar. Injection sites containing as few as 10(5) MSCs could be detected and contained intact IFP-bearing MSCs on histology.IFP labeling of MSCs imparts useful MRI contrast, enabling ready detection in the beating heart on a conventional cardiac MR scanner after transplantation into normal and infarcted myocardium. The dual-labeled MSCs can be identified at locations corresponding to injection sites, both ex vivo using fluorescence microscopy and in vivo using susceptibility contrast on MRI. This technology may permit effective in vivo study of stem cell retention, engraftment, and migration.
Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology
Authors: Véronique Laithier, Jacques Grill, Marie-Cécile Le Deley, Marie-Madeleine Ruchoux, Dominique Couanet, François Doz, Fabienne Pichon, Hervé Rubie, Didier Frappaz, Jean-Paul Vannier, Annie Babin-Boilletot, Eric Sariban, Pascal Chastagner, Michel Zerah, Marie-Anne Raquin, Olivier Hartmann, Chantal Kalifa
Journal: Journal of Clinical Oncology (2003)

To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months.Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy.Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P =.047) and absence of neurofibromatosis type 1 (P =.035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P =.0053) and no objective response to chemotherapy (P =.0029). Three-year PFS was 44% in infants < or = 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR.A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.
Role of Gallbladder Mucin in Pathophysiology of Gallstones
Authors: Thomas J. Lamont, Bernard F. Smith, James R. L. Moore
Journal: Hepatology (1984)

A critical step in the formation of cholesterol gallstones is nucleation (i.e., the formation of cholesterol monohydrate crystals from supersaturated bile). The rate of nucleation of cholesterol depends upon a critical balance between pronucleating and antinucleating factors in bile. Mucin, a high molecular weight glycoprotein secreted by the gallbladder and biliary duct epithelium, is a pronucleating agent in experimental and human gallstone disease. Gallbladder mucin shares with other epithelial mucins the ability to bind lipids and bile pigment. The hydrophobic binding sites in the polypeptide core of mucin may provide a favorable environment for nucleation of cholesterol monohydrate from supersaturated bile. In nearly all animal models of cholelithiasis, mucin hypersecretion is prominent. The stimulus for gallbladder mucin hypersecretion appears to be a component of lithogenic bile. Prostaglandins regulate mucin release in gallbladder epithelium in vitro and probably in vivo. In the cholesterol-fed prairie dog, blockage of mucin release with aspirin inhibits gallstone formation. These findings suggest that inhibition of mucin release may prevent cholesterol stone formation during high-risk periods or after dissolution therapy with bile salts.
Association of a Promoter Polymorphism of the CD14 Gene and Atopy
Authors: GERARD H. KOPPELMAN, NAOMI E. REIJMERINK, O. COLIN STINE, TIMOTHY D. HOWARD, PAUL A. WHITTAKER, DEBORAH A. MEYERS, DIRKJE S. POSTMA, EUGENE R. BLEECKER
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Atopy is generally considered to be caused by interaction of genetic and environmental factors. Recently, an association of a C-to-T transition in the promoter region of the CD14 gene on chromosome 5q31.1 and atopic phenotypes was reported in a population study of school children in the United States. The aim of the present study was to investigate the association of the C allele of the CD14/ − 159 with phenotypes of atopy and asthma in an adult Dutch population in which linkage of total serum IgE and bronchial hyperresponsiveness to chromosome 5q31–33 is present. We studied 159 probands with asthma and 158 spouses as controls. Phenotypes for asthma (e.g., bronchial hyperresponsiveness, physician's diagnosis) and for atopy (e.g., total serum IgE level, intracutaneous skin test, allergic rhinitis) were studied. In this population, homozygotes for the C allele had a higher number of positive skin tests and higher total serum IgE levels (in skin test-positive individuals) and subsequently, more self-reported allergic symptoms including rhinitis and hay fever, compared with subjects with CT and TT alleles. We conclude that the − 159 C-to-T promoter polymorphism in the CD14 gene may result in expression of a more severe allergic phenotype.
Selective loss of glucocerebrosidase activity in sporadic Parkinson’s disease and dementia with Lewy bodies
Authors: Davide Chiasserini, Silvia Paciotti, Paolo Eusebi, Emanuele Persichetti, Anna Tasegian, Marzena Kurzawa-Akanbi, Patrick F Chinnery, Christopher M Morris, Paolo Calabresi, Lucilla Parnetti, Tommaso Beccari
Journal: Molecular Neurodegeneration (2015)

Lysosomal dysfunction is thought to be a prominent feature in the pathogenetic events leading to Parkinson's disease (PD). This view is supported by the evidence that mutations in GBA gene, coding the lysosomal hydrolase β-glucocerebrosidase (GCase), are a common genetic risk factor for PD. Recently, GCase activity has been shown to be decreased in substantia nigra and in cerebrospinal fluid of patients diagnosed with PD or dementia with Lewy Bodies (DLB). Here we measured the activity of GCase and other endo-lysosomal enzymes in different brain regions (frontal cortex, caudate, hippocampus, substantia nigra, cerebellum) from PD (n = 26), DLB (n = 16) and age-matched control (n = 13) subjects, screened for GBA mutations. The relative changes in GCase gene expression in substantia nigra were also quantified by real-time PCR. The role of potential confounders (age, sex and post-mortem delay) was also determined. Substantia nigra showed a high activity level for almost all the lysosomal enzymes assessed. GCase activity was significantly decreased in the caudate (−23%) and substantia nigra (−12%) of the PD group; the same trend was observed in DLB. In both groups, a decrease in GCase mRNA was documented in substantia nigra. No other lysosomal hydrolase defects were determined. The high level of lysosomal enzymes activity observed in substantia nigra, together with the selective reduction of GCase in PD and DLB patients, further support the link between lysosomal dysfunction and PD pathogenesis, favoring the possible role of GCase as biomarker of synucleinopathy. Mapping the lysosomal enzyme activities across different brain areas can further contribute to the understanding of the role of lysosomal derangement in PD and other synucleinopathies.
Mutation-Specific Antibodies for the Detection of <i>EGFR</i> Mutations in Non–Small-Cell Lung Cancer
Authors: Jian Yu, Susan Kane, Jiong Wu, Elisa Benedettini, Daiqiang Li, Cynthia Reeves, Gregory Innocenti, Randy Wetzel, Katherine Crosby, Alison Becker, Michelle Ferrante, Wan Cheung Cheung, Xiqiang Hong, Lucian R. Chirieac, Lynette M. Sholl, Herbert Haack, Bradley L. Smith, Roberto D. Polakiewicz, Yi Tan, Ting-Lei Gu, Massimo Loda, Xinmin Zhou, Michael J. Comb
Journal: Clinical Cancer Research (2009)

Activating mutations within the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are found in approximately 10% to 20% of non-small-cell lung cancer (NSCLC) patients and are associated with response to EGFR inhibitors. The most common NSCLC-associated EGFR mutations are deletions in exon 19 and L858R mutation in exon 21, together accounting for 90% of EGFR mutations. To develop a simple, sensitive, and reliable clinical assay for the identification of EGFR mutations in NSCLC patients, we generated mutation-specific rabbit monoclonal antibodies against each of these two most common EGFR mutations and aimed to evaluate the detection of EGFR mutations in NSCLC patients by immunohistochemistry.We tested mutation-specific antibodies by Western blot, immunofluorescence, and immunohistochemistry. In addition, we stained 40 EGFR genotyped NSCLC tumor samples by immunohistochemistry with these antibodies. Finally, with a panel of four antibodies, we screened a large set of NSCLC patient samples with unknown genotype and confirmed the immunohistochemistry results by DNA sequencing.These two antibodies specifically detect the corresponding mutant form of EGFR by Western blotting, immunofluorescence, and immunohistochemistry. Screening a panel of 340 paraffin-embedded NSCLC tumor samples with these antibodies showed that the sensitivity of the immunohistochemistry assay is 92%, with a specificity of 99% as compared with direct and mass spectrometry-based DNA sequencing.This simple assay for detection of EGFR mutations in diagnostic human tissues provides a rapid, sensitive, specific, and cost-effective method to identify lung cancer patients responsive to EGFR-based therapies.
Clinical Aspects of Neuroimmunology
Authors: F. C. Rose
Journal: Annals of the Rheumatic Diseases (1980)

narrow-spectrum drugs does not convey the fact that co-trimoxazole or amoxycillin are the drugs of choice in the treatment of most chest infections in patients with sex-linked or late-onset hypogammaglobulinaemia.The suggestion that pentamidine might be used in the prophylaxis of Pneumocystis carinii pneumonia is wrong.In fact, co-trimoxazole is the only drug suitable for prophylaxis and is the drug of choice for treatment.The section on malignancy makes the important point that the raised incidence occurs mainly in patients with ataxia telangiectasia and Wiskott-Aldrich syndrome.British experience does not bear out the comment that 6-9 % of patients with sex-linked hypogammaglobulinaemia develop tumours.The old WHO term of 'common variable immunodeficiency' has now been changed to 'varied immunodeficiency.'The reviewer believes that most of the patients previously described under this heading should now be described under the term 'late-onset hypogammaglobulinaemia.'This refers to patients with hypogammaglobulinaemia of unknown aetiology affecting IgG and IgA and usually IgM, which starts after the first 2 years of life with a normal percentage of T cells by E rosetting.Some of the conclusions are debatable.Gammaglobulin injections have been disappointing in the treatment of selective IgA deficiency, This removes much of the value in preparing gammaglobulin for injection which is free from IgA.