tbuckley/cabot-search huggingface dataset:
Comparison of nine theoretical models for estimating the mechanical power output in cycling * COMMENTARY
Authors: Carlos González-Haro, P A Galilea Ballarini, M Soria, F Drobnic, J F Escanero
Journal: British Journal of Sports Medicine (2007)

Objective: To assess which of the equations used to estimate mechanical power output for a wide aerobic range of exercise intensities gives the closest value to that measured with the SRM training system. Methods: Thirty four triathletes and endurance cyclists of both sexes (mean (SD) age 24 (5) years, height 176.3 (6.6) cm, weight 69.4 (7.6) kg and V o 2 max 61.5 (5.9) ml/kg/min) performed three incremental tests, one in the laboratory and two in the velodrome. The mean mechanical power output measured with the SRM training system in the velodrome tests corresponding to each stage of the tests was compared with the values theoretically estimated using the nine most referenced equations in literature (Whitt ( Ergonomics 1971;14:419–24); Di Prampero et al ( J Appl Physiol 1979;47:201–6); Whitt and Wilson ( Bicycling science . Cambridge: MIT Press, 1982); Kyle ( Racing with the sun . Philadelphia: Society of Automotive Engineers, 1991:43–50); Menard (First International Congress on Science and Cycling Skills, Malaga, 1992); Olds et al ( J Appl Physiol 1995;78:1596–611; J Appl Physiol 1993;75:730–7); Broker ( USOC Sport Science and Technology Report 1–24, 1994); Candau et al ( Med Sci Sports Exerc 1999;31:1441–7)). This comparison was made using the mean squared error of prediction, the systematic error and the random error. Results: The equations of Candau et al , Di Prampero et al , Olds et al ( J Appl Physiol 1993;75:730–7) and Whitt gave a moderate mean squared error of prediction (12.7%, 21.6%, 13.2% and 16.5%, respectively) and a low random error (0.5%, 0.6%, 0.7% and 0.8%, respectively). Conclusions: The equations of Candau et al and Di Prampero et al give the best estimate of mechanical power output when compared with measurements obtained with the SRM training system.
In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. IV. Cytotoxic effect of an anti-T11-gelonin immunotoxin.
Authors: K A Reimann, V S Goldmacher, J M Lambert, L V Chalifoux, S B Cook, S F Schlossman, N L Letvin
Journal: Journal of Clinical Investigation (1988)

The cytotoxic effect of a lymphocyte-specific immunotoxin formed by disulfide conjugation of an anti-T11 monoclonal antibody with the ribosome-inactivating protein gelonin was assessed in vitro on peripheral blood T cells and in vivo on splenic and lymph node T cells of macaque monkeys. This immunotoxin was cytotoxic to proliferating peripheral blood T cells in vitro as measured by both direct and indirect assays. Two sequential intravenous infusions into macaque monkeys achieved plasma concentrations of immunotoxin far in excess of those shown to be cytotoxic for cultured T cells and coated all T cells in lymph nodes and spleen with intact immunotoxin for four days. However, the cytotoxic effect of the immunotoxin on T cells in vivo was considerably less than that predicted by the in vitro studies. Further experiments suggested that the state of activation of the targeted T cell population in vivo, or the appearance of anti-immunotoxin antibodies, which occurred in all infused monkeys, might attenuate immunotoxin-mediated cell killing in vivo. These studies illustrate the significant differences between the action of immunotoxin conjugates in vitro, and those seen when these conjugates are utilized as therapeutic agents in vivo.
Contrasting Patterns of Evolution of 45S and 5S rDNA Families Uncover New Aspects in the Genome Constitution of the Agronomically Important Grass Thinopyrum intermedium (Triticeae)
Authors: Václav Mahelka, David Kopecký, Bernard R. Baum
Journal: Molecular Biology and Evolution (2013)

We employed sequencing of clones and in situ hybridization (genomic and fluorescent in situ hybridization [GISH and rDNA-FISH]) to characterize both the sequence variation and genomic organization of 45S (herein ITS1-5.8S-ITS2 region) and 5S (5S gene + nontranscribed spacer) ribosomal DNA (rDNA) families in the allohexaploid grass Thinopyrum intermedium. Both rDNA families are organized within several rDNA loci within all three subgenomes of the allohexaploid species. Both families have undergone different patterns of evolution. The 45S rDNA family has evolved in a concerted manner: internal transcribed spacer (ITS) sequences residing within the arrays of two subgenomes out of three got homogenized toward one major ribotype, whereas the third subgenome contained a minor proportion of distinct unhomogenized copies. Homogenization mechanisms such as unequal crossover and/or gene conversion were coupled with the loss of certain 45S rDNA loci. Unlike in the 45S family, the data suggest that neither interlocus homogenization among homeologous chromosomes nor locus loss occurred in 5S rDNA. Consistently with other Triticeae, the 5S rDNA family in intermediate wheatgrass comprised two distinct array types—the long- and short-spacer unit classes. Within the long and short units, we distinguished five and three different types, respectively, likely representing homeologous unit classes donated by putative parental species. Although the major ITS ribotype corresponds in our phylogenetic analysis to the E-genome species, the minor ribotype corresponds to Dasypyrum. 5S sequences suggested the contributions from Pseudoroegneria, Dasypyrum, and Aegilops. The contribution from Aegilops to the intermediate wheatgrass' genome is a new finding with implications in wheat improvement. We discuss rDNA evolution and potential origin of intermediate wheatgrass.
Animal models of chronic obstructive pulmonary disease
Authors: P A Dawkins
Journal: Thorax (2001)

Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in the UK,1 causing 26 000 deaths and 240 000 hospital admissions and costing the NHS £486 million per annum. It is also a global problem, reaching almost epidemic proportions in the developing world. Despite this, it receives relatively little attention compared with diseases with a similar impact such as coronary heart disease and cancer. The research into new treatments to prevent the development and progression of this condition presents a major challenge. It is thus important to develop tools that can both direct development of new drugs and provide insights into assessment of their efficacy before extensive human trials are undertaken.

Animal models act as a bridge between in vitro studies in the laboratory and studies in humans. As such, they have had a major impact on the investigation of many medical conditions. In COPD, in particular, animal models would enable basic research to investigate the mechanisms of inflammatory cell recruitment and abnormal matrix repair (the proteinase/antiproteinase hypothesis2) and alternative hypotheses of the pathogenesis of emphysema such as those implicating lung cell apoptosis as a primary event.3 They would also facilitate the testing of new treatments such as gene therapy (in cystic fibrosis and α1-antitrypsin deficiency (A1AT)) and “designer drugs” targeting specific cytokines or biochemical pathways. By leading to a clearer understanding of the key events in the pathophysiology of COPD and enabling short term studies to develop appropriate strategies, animal models can provide a framework for the rational and safe design of expensive and long term clinical studies.

The mouse provides the best choice for an animal model4 because the mouse genome has been extensively studied and sequenced and close similarities exist with the human genome. In addition, complementary antibodies and probes …
Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line.
Authors: A H Gorn, H Y Lin, M Yamin, P E Auron, M R Flannery, D R Tapp, C A Manning, H F Lodish, S M Krane, S R Goldring
Journal: Journal of Clinical Investigation (1992)

A human ovarian small cell carcinoma line (BIN-67) expresses abundant calcitonin (CT) receptors (CTR) (143,000 per cell) that are coupled, to adenylate cyclase. The dissociation constants (Kd) for the CTRs on these BIN-67 cells is approximately 0.42 nM for salmon CT and approximately 4.6 nM for human CT. To clone a human CTR (hCTR), a BIN-67 cDNA library was screened using a cDNA probe from a porcine renal CTR (pCTR) that we recently cloned. One positive clone of 3,588 bp was identified. Transfection of this cDNA into COS cells resulted in expression of receptors with high affinity for salmon CT (Kd = approximately 0.44 nM) and for human CT (Kd = approximately 5.4 nM). The expressed hCTR was coupled to adenylate cyclase. Northern analysis with the hCTR cDNA probe indicated a single transcript of approximately 4.2 kb. The cloned cDNA encodes a putative peptide of 490 amino acids with seven potential transmembrane domains. The amino acid sequence of the hCTR is 73% identical to the pCTR, although the hCTR contains an insert of 16 amino acids between transmembrane domain I and II. The structural differences may account for observed differences in binding affinity between the porcine renal and human ovarian CTRs. The CTRs are closely related to the receptors for parathyroid hormone-parathyroid hormone-related peptide and secretin; these receptors comprise a distinct family of G protein-coupled seven transmembrane domain receptors. Interestingly, the hCTR sequence is remotely related to the cAMP receptor of Dictyostelium discoideum (21% identical), but is not significantly related to other G protein-coupled receptor sequences now in the data bases.
Aortic Arteriosclerosis in the Dog After Localized Aortic Irradiation with Electrons
Authors: Stuart Lindsay, Cecil Entenman, Eldon E. Ellis, Charles L. Geraci
Journal: Circulation Research (1962)

The distal segments of the abdominal aortas of 15 dogs were irradiated with electrons in doses ranging from 1,000 to 9,500 rads and were examined histologically at intervals ranging from 2 weeks to 17 months following irradiation. Pronounced aortic arteriosclerosis developed and was sharply localized to the aortic segment irradiated. Except in one dog, radiation-induced arteriosclerosis was more pronounced on the dorsal than on the ventral aortic wall. There was no evidence that severity of aortic arteriosclerosis was related to the dose of irradiation or was increased with time following irradiation. The development of arteriosclerotic lesions of the aorta induced by electron irradiation was similar to that observed after x-irradiation and to that occurring naturally in old dogs. It is suggested that electron irradiation may have caused selective injury of the internal elastic lamina, which was then followed by intimal fibrous proliferation and formation of intimal plaques.
Functionalization of Tumor Necrosis Factor-α Using Phage Display Technique and PEGylation Improves Its Antitumor Therapeutic Window
Authors: Hiroko Shibata, Yasuo Yoshioka, Shinji Ikemizu, Kyoko Kobayashi, Yoko Yamamoto, Yohei Mukai, Takayuki Okamoto, Madoka Taniai, Maki Kawamura, Yasuhiro Abe, Shinsaku Nakagawa, Takao Hayakawa, Satoshi Nagata, Yuriko Yamagata, Tadanori Mayumi, Haruhiko Kamada, Yasuo Tsutsumi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In this study, the optimization of antitumor therapy with tumor necrosis factor-α (TNF-α) was attempted. Experimental Design: Using the phage display technique, we created a lysine-deficient mutant TNF-α (mTNF-K90R). This mutant had higher affinities to both TNF receptors, despite reports that certain lysine residues play important roles in trimer formation and receptor binding. Results: The mTNF-K90R showed an in vivo therapeutic window that was 13-fold higher than that of the wild-type TNF-α (wTNF-α). This was due to the synergistic effect of its 6-fold stronger in vitro bioactivity and its 2-fold longer plasma half-life derived from its surface negative potential. The reason why the mTNF-K90R showed a higher bioactivity was understood by a molecular modeling analysis of the complex between the wTNF-α and TNF receptor-I. The mTNF-K90R, which was site-specifically mono-PEGylated at the NH2 terminus (sp-PEG-mTNF-K90R), had a higher in vitro bioactivity and considerably longer plasma half-life than the wTNF-α, whereas the randomly mono-PEGylated wTNF-α had 6% of the bioactivity of the wTNF-α. With regard to effectiveness and safety, the in vivo antitumor therapeutic window of the sp-PEG-mTNF-K90R was 60-fold wider than that of the wTNF-α. Conclusions: These results indicated that this functionalized TNF-α may be useful not only as an antitumor agent but also as a selective enhancer of vascular permeability in tumors for improving antitumor chemotherapy.
Quantitative genomics of locomotor behavior in Drosophila melanogaster
Authors: Katherine W Jordan, Mary Anna Carbone, Akihiko Yamamoto, Theodore J Morgan, Trudy FC Mackay
Journal: Genome biology (2007)

Abstract Background Locomotion is an integral component of most animal behaviors, and many human health problems are associated with locomotor deficits. Locomotor behavior is a complex trait, with population variation attributable to many interacting loci with small effects that are sensitive to environmental conditions. However, the genetic basis of this complex behavior is largely uncharacterized. Results We quantified locomotor behavior of Drosophila melanogaster in a large population of inbred lines derived from a single natural population, and derived replicated selection lines with different levels of locomotion. Estimates of broad-sense and narrow-sense heritabilities were 0.52 and 0.16, respectively, indicating substantial non-additive genetic variance for locomotor behavior. We used whole genome expression analysis to identify 1,790 probe sets with different expression levels between the selection lines when pooled across replicates, at a false discovery rate of 0.001. The transcriptional responses to selection for locomotor, aggressive and mating behavior from the same base population were highly overlapping, but the magnitude of the expression differences between selection lines for increased and decreased levels of behavior was uncorrelated. We assessed the locomotor behavior of ten mutations in candidate genes with altered transcript abundance between selection lines, and identified seven novel genes affecting this trait. Conclusion Expression profiling of genetically divergent lines is an effective strategy for identifying genes affecting complex behaviors, and reveals that a large number of pleiotropic genes exhibit correlated transcriptional responses to multiple behaviors.
Microbiome dynamics of human epidermis following skin barrier disruption
Authors: Patrick LJM Zeeuwen, Jos Boekhorst, Ellen H van den Bogaard, Heleen D de Koning, Peter MC van de Kerkhof, Delphine M Saulnier, Iris I van Swam, Sacha AFT van Hijum, Michiel Kleerebezem, Joost Schalkwijk, Harro M Timmerman
Journal: Genome biology (2012)

Abstract Background Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury. Results We observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes. Conclusions We suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer, may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue, will shed further light on the complex interaction between resident bacteria and epidermis.
Repuncturing the Renal Biopsy
Authors: Matthias Kretzler, Clemens D. Cohen, Peter Doran, Anna Henger, Stephen Madden, Elisabeth F. Gro[Combining Diaeresis]ne, Peter J. Nelson, Detlef Schlo[Combining Diaeresis]ndorff, Hermann-Josef Gro[Combining Diaeresis]ne
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. As has been exemplified by recent progress in the classification of cancer, future approaches to enhance the clinical diagnostic power of tissue biopsies may be based on gene expression profiles. A series of strategies to translate these approaches to the diagnosis of renal disease is here proposed. The theoretical and technical problems resulting from the small amount of starting material available from renal biopsies will be specifically addressed. A preliminary study with cDNA array-based expression data obtained from kidneys with tubulointerstitial inflammation and fibrosis suggests the feasibility of distinguishing molecular categories of renal disease. Finally, a combined conventional and molecular work-up of renal biopsies will be suggested. These approaches should add a new dimension to biopsy interpretation and provide novel information concerning renal pathogenesis, diagnosis, prognosis, and differential therapy. A coordinated effort from nephrologists and pathologists in large multicenter trials will be required to achieve this goal. It is hoped that this outlook will lead to stimulating discussions and the implementation of these innovative ideas in nephrology.
Soluble Complement Receptor-1 Protects Heart, Lung, and Cardiac Myofilament Function From Cardiopulmonary Bypass Damage
Authors: Paul J. Chai, Rashid Nassar, Annette E. Oakeley, Damian M. Craig, George Quick, James Jaggers, Stephen P. Sanders, Ross M. Ungerleider, Page A. W. Anderson
Journal: Circulation (2000)

Background —Host defense system activation occurs with cardiopulmonary bypass (CPB) and is thought to contribute to the pathophysiological consequences of CPB. Complement inhibition effects on the post-CPB syndrome were tested with soluble complement receptor-1 (sCR1). Methods and Results —Twenty neonatal pigs (weight 1.8 to 2.8 kg) were randomized to control and sCR1-treated groups. LV pressure and volume, left atrial pressure, pulmonary artery pressure and flow, and respiratory system compliance and resistance were measured. Preload recruitable stroke work, isovolumic diastolic relaxation time constant (τ), and pulmonary vascular resistance were determined. Pre-CPB measures were not statistically significantly different between the 2 groups. After CPB, preload recruitable stroke work was significantly higher in the sCR1 group (n=5, 46.8±3.2×10 3 vs n=6, 34.3±3.7×10 3 erg/cm 3 , P =0.042); τ was significantly lower in the sCR1 group (26.4±1.5, 42.4±6.6 ms, P =0.003); pulmonary vascular resistance was significantly lower in the sCR1 group (5860±1360 vs 12 170±1200 dyn · s/cm 5 , P =0.009); arterial P o 2 in 100% F io 2 was significantly higher in the sCR1 group (406±63 vs 148±33 mm Hg, P =0.01); lung compliance and airway resistance did not differ significantly. The post-CPB Hill coefficient of atrial myocardium was higher in the sCR1 group (2.88±0.29 vs 1.88±0.16, P =0.023). Conclusions —sCR1 meaningfully moderates the post-CPB syndrome, supporting the hypothesis that complement activation contributes to this syndrome.
STUDIES OF ADRENAL CORTICAL ACTIVITY IN PSYCHONEUROTIC SUBJECTS
Authors: R. A. CLEGHORN, B. F. GRAHAM
Journal: American Journal of Psychiatry (1950)

The use of a cumulative index of adrenal cortical activity has been described. This has been applied to the estimation of adrenocortical activity after (1) small doses of ACTH in anxiety states, (2) injection of saline and venipuncture, (3) controlled thermal pain, and (4) electroconvulsive therapy. In all these experiments the data indicate activation of the adrenal cortex. It is suggested that the greater the patient's anxiety and tenseness the greater the activation of the adrenal cortex by the test situation. The use of pretreatment sodium amytal seems to decrease the response of the adrenal cortex to ECT.
Prognostic Value of Intratumoral Interferon Gamma Messenger RNA Expression in Invasive Cervical Carcinomas
Authors: Eric Tartour, Alain Gey, Wolf H. Fridman, Xavier Sastre-Garau, Isabelle Lombard Surin, Véronique Mosseri
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The production of the cytokine interferon gamma (IFN γ) by activated peripheral blood mononuclear cells may be reduced in patients with invasive cervical carcinoma. This study was designed to assess the prognostic value of intratumoral IFN γ messenger RNA (mRNA) levels in such patients. Methods: Biopsy specimens of primary cervical lesions were obtained from 27 patients with invasive squamous cell carcinoma before they received any therapy. Two prognostic groups were considered: 1) a group of 14 patients who had no apparent disease recurrence and who were alive 2 years after diagnosis (good-prognosis group) and 2) a group of 13 patients who had disease recurrence or died during the 2-year follow-up (poor-prognosis group). A competitive reverse transcription-polymerase chain reaction assay was used to measure levels of IFN γ and β actin mRNA. The expression of human leukocyte antigen (HLA) class II proteins (which is stimulated by IFN γ) in tumor cells was studied by immunostaining. Results: Tumor specimens from all 14 patients in the good-prognosis group contained more than 103 IFN γ mRNA copies per 5 × 105 β actin mRNA copies, whereas tumor specimens from only six of the 13 patients in the poor-prognosis group contained this level of IFN γ mRNA (two-sided P = .006). No clear relationship was observed between levels of IFN γ mRNA and T-cell or natural killer cell infiltration in tumors; however, a statistically significant association was observed between HLA class II expression on tumor cells and IFN γ mRNA levels (two-sided P = .01). Conclusions: A subgroup of poor-prognosis cervical carcinoma patients who have low levels of intratumoral IFN γ mRNA was identified.
A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia
Authors: Stephen J Huffaker, Jingshan Chen, Kristin K Nicodemus, Fabio Sambataro, Feng Yang, Venkata Mattay, Barbara K Lipska, Thomas M Hyde, Jian Song, Dan Rujescu, Ina Giegling, Karine Mayilyan, Morgan J Proust, Armen Soghoyan, Grazia Caforio, Joseph H Callicott, Alessandro Bertolino, Andreas Meyer-Lindenberg, Jay Chang, Yuanyuan Ji, Michael F Egan, Terry E Goldberg, Joel E Kleinman, Bai Lu, Daniel R Weinberger
Journal: Nature Medicine (2009)