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1
Sørensen, John Dalsgaard. „Framework for risk-based planning of operation and maintenance for offshore wind turbines“. Wind Energy 12, Nr. 5 (Juli 2009): 493–506. http://dx.doi.org/10.1002/we.344.
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Boldyrev, Vladimir V. „Reactivity of solids. Where are we now?“ Annales de chimie Science des Matériaux 34, Nr. 6 (28.12.2009): 337–44. http://dx.doi.org/10.3166/acsm.34.337-344.
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Jeyaraju, Danny V., Rose Hurren, Xiaoming Wang, Neil MacLean, Marcela Gronda, Craig T. Jordan, Mark D. Minden, Guri Giaever und Aaron D. Schimmer. „A Novel Isoflavone, ME-344, Targets the Cytoskeleton in Acute Myeloid Leukemia“. Blood 126, Nr. 23 (03.12.2015): 3682. http://dx.doi.org/10.1182/blood.v126.23.3682.3682.
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Abstract The isoflavone ME-344 is a potent anti-cancer agent with preclinical efficacy in solid tumors in vitro and in vivo. In a recently completed phase I clinical trial in patients with refractory solid tumors, ME-344 was well tolerated and clinical responses in refractory patients were observed. ME-344 has been shown to reduce mitochondrial ATP generation in a tumor selective manner, though other potential activities have not been fully defined. In addition, the preclinical efficacy of ME-344 in leukemia has not been established. Therefore, we investigated the anti-leukemic properties and the mechanism of action of ME-344. We treated a panel of 7 leukemia cell lines with increasing concentrations of ME-344, and measured cell growth and viability. ME-344 was cytotoxic to the 7 leukemia cell lines with an IC50 in the range of 70-260 nM. In addition, ME-344 induced preferential death in primary AML patient samples over normal hematopoietic cells. In an OCI-AML2 xenograft model, ME-344 reduced tumor growth by up to 95% of control without evidence of toxicity. Mechanistically, as reported in studies in solid tumors, ME-344 increased mitochondrial ROS generation in leukemic cells. However, antioxidant treatment did not rescue cell death, suggesting that ME-344 has additional targets beyond the mitochondria. To identify additional targets of ME-344, we conducted haplo-insufficiency profiling in S.cerevisiae to identify genes whose heterozygous deletion confers increased sensitivity to ME-344. The top hits from the screen were genes involved in cytoskeletal organization. Therefore, we tested the effects of ME-344 on actin and tubulin polymerization in cell free assays. While ME-344 did not inhibit actin polymerization, it inhibited tubulin polymerization by interacting near the colchicine-binding site and at a site distinct from vinca alkaloids. Furthermore, cells resistant to tubulin inhibitors due to tubulin point mutations were also resistant to ME-344. Finally, we showed that ME-344 synergizes with vinblastine in leukemia cells. Thus, our study demonstrates that ME-344 displays preclinical efficacy in leukemia through a mechanism at least partly related to targeting tubulin polymerization. Disclosures No relevant conflicts of interest to declare.
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Ginzburg, M. „I. The Indigestion of breast Babies II. Artificial feeding of Infants III. How shall we feed the Baby“. Journal of obstetrics and women's diseases 11, Nr. 3 (22.12.2020): 340–44. http://dx.doi.org/10.17816/jowd113340-344.
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Hovinga, JK, J. Schaller, H. Stricker, WA Wuillemin, M. Furlan und B. Lammle. „Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallikrein cleavage site“. Blood 84, Nr. 4 (15.08.1994): 1173–81. http://dx.doi.org/10.1182/blood.v84.4.1173.1173.
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Abstract The dysfunctional coagulation factor XII (FXII) Locarno was purified from 2 L of the proposita's plasma. Studies to identify the molecular defect responsible for the lack of amidolytic and proteolytic activity of this FXII variant were performed. Amino acid sequence analysis of peptides obtained from FXII Locarno on activation with either trypsin or plasma kallikrein and dextran sulfate showed an amino acid substitution of Arg 353 by Pro. Thereby, the kallikrein cleavage site at Arg 353-Val 354 is lost. Although trypsin-activated FXII Locarno was fully cleaved at Arg 334-Asn 335 and at Arg 343-Leu 344, neither amidolytic nor proteolytic activity was generated. We conclude that proteolytic cleavage at Arg 343 in the absence of cleavage at Arg 353 is not sufficient to expose the enzymatic active site in FXII Locarno.
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Hovinga, JK, J. Schaller, H. Stricker, WA Wuillemin, M. Furlan und B. Lammle. „Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallikrein cleavage site“. Blood 84, Nr. 4 (15.08.1994): 1173–81. http://dx.doi.org/10.1182/blood.v84.4.1173.bloodjournal8441173.
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The dysfunctional coagulation factor XII (FXII) Locarno was purified from 2 L of the proposita's plasma. Studies to identify the molecular defect responsible for the lack of amidolytic and proteolytic activity of this FXII variant were performed. Amino acid sequence analysis of peptides obtained from FXII Locarno on activation with either trypsin or plasma kallikrein and dextran sulfate showed an amino acid substitution of Arg 353 by Pro. Thereby, the kallikrein cleavage site at Arg 353-Val 354 is lost. Although trypsin-activated FXII Locarno was fully cleaved at Arg 334-Asn 335 and at Arg 343-Leu 344, neither amidolytic nor proteolytic activity was generated. We conclude that proteolytic cleavage at Arg 343 in the absence of cleavage at Arg 353 is not sufficient to expose the enzymatic active site in FXII Locarno.
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Han, Nanyu, Justin Tze Yang Ng, Yanpeng Li, Yuguang Mu und Zunxi Huang. „Plasticity of the 340-Loop in Influenza Neuraminidase Offers New Insight for Antiviral Drug Development“. International Journal of Molecular Sciences 21, Nr. 16 (06.08.2020): 5655. http://dx.doi.org/10.3390/ijms21165655.
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The recently discovered 340-cavity in influenza neuraminidase (NA) N6 and N7 subtypes has introduced new possibilities for rational structure-based drug design. However, the plasticity of the 340-loop (residues 342–347) and the role of the 340-loop in NA activity and substrate binding have not been deeply exploited. Here, we investigate the mechanism of 340-cavity formation and demonstrate for the first time that seven of nine NA subtypes are able to adopt an open 340-cavity over 1.8 μs total molecular dynamics simulation time. The finding that the 340-loop plays a role in the sialic acid binding pathway suggests that the 340-cavity can function as a druggable pocket. Comparing the open and closed conformations of the 340-loop, the side chain orientation of residue 344 was found to govern the formation of the 340-cavity. Additionally, the conserved calcium ion was found to substantially influence the stability of the 340-loop. Our study provides dynamical evidence supporting the 340-cavity as a druggable hotspot at the atomic level and offers new structural insight in designing antiviral drugs.
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Alberto, Maria K. „Ready Reader One: The Stories We Tell With, About, and Around Videogames, Megan Amber Condis and Mike Sell (eds) (2024)“. Journal of Gaming & Virtual Worlds 16, Nr. 3 (01.09.2024): 387–90. https://doi.org/10.1386/jgvw_00111_5.
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Review of: Ready Reader One: The Stories We Tell With, About, and Around Videogames, Megan Amber Condis and Mike Sell (eds) (2024) Baton Rouge, LA: Louisiana State University Press, 344 pp., ISBN 978-0-80718-230-7, p/bk, USD 35.00
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Aguirre, J. I., N. W. Morrell, L. Long, P. Clift, P. D. Upton, J. M. Polak und M. R. Wilkins. „Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia“. American Journal of Physiology-Lung Cellular and Molecular Physiology 278, Nr. 5 (01.05.2000): L981—L987. http://dx.doi.org/10.1152/ajplung.2000.278.5.l981.
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Chronic hypoxia leads to a greater degree of pulmonary hypertension in the Wistar-Kyoto (WKY) rat than in the Fischer 344 (F-344) rat. We questioned whether this difference is associated with baseline differences in pulmonary artery anatomy, a greater degree of hypoxia-induced pulmonary vascular remodeling in the WKY rat, and/or differences in expression of endothelin (ET)-1. Male F-344 and WKY rats were maintained in normoxia or normobaric hypoxia for 21 days. Morphometry revealed that baseline pulmonary artery anatomy was similar in the two strains. However, during chronic hypoxia, the WKY rats developed a greater degree of muscularization of small pulmonary arteries. Baseline plasma and lung immunoreactive ET-1 levels were similar in the WKY and F-344 rats and increased significantly during hypoxia in the WKY rats. Northern analysis demonstrated increased lung preproET-1 mRNA during hypoxia in both strains, with a greater increase in WKY rats. Immunostaining demonstrated increased ET-1 in bronchial epithelium and peripheral pulmonary arteries during hypoxia, although to a greater degree in the WKY rats. We conclude that the WKY strain demonstrates increased susceptibility to hypoxia-induced pulmonary vascular remodeling compared with the F-344 strain and that increased lung and circulating ET-1 levels during hypoxia may partly explain this difference.
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Yang, X. X., W. S. Powell, L. J. Xu und J. G. Martin. „Strain dependence of the airway response to dry-gas hyperpnea challenge in the rat“. Journal of Applied Physiology 86, Nr. 1 (01.01.1999): 152–58. http://dx.doi.org/10.1152/jappl.1999.86.1.152.
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The aim of the study was to investigate strain dependence and mechanisms of airway responses to dry-gas hyperpnea challenge in the rat. We studied responses in a strain that is hyperresponsive to methacholine, Fischer 344 (F-344); in two normoresponsive strains, Lewis and ACI; and in an atopic but normoresponsive strain, Brown Norway (BN). We examined the effects of a neurokinin (NK) 1-receptor (CP-99994), an NK2-receptor (SR-48968), and a leukotriene D4(LTD4)-receptor antagonist (pranlukast) on responses to hyperpnea challenge in BN rats. The animals were ventilated with a tidal volume of 8 ml/kg and a frequency of 150 breaths/min with either a dry or humidified mixture of 5% CO2-95% O2 for 5 min for hyperpnea challenge, whereas responses to challenge were measured during spontaneous breathing. Pulmonary resistance increased after dry-gas challenge in BN and ACI but not in F-344 and Lewis rats. CP-99994, SR-48968, and pranlukast significantly attenuated the increase in pulmonary resistance after dry-gas challenge. There were no significant differences in responsiveness to airway challenge with LTD4 among the BN, F-344 and ACI rats. We conclude that responses to dry-gas hyperpnea challenge are strain dependent in rats and are mediated by NKs and LTD4.
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Uzun, S., O. Kozumplik und V. Folnegovic-Smalc. „344 – Patients with manic episode with aggression as dominant symptom: What can we do?“ Schizophrenia Research 98 (Februar 2008): 175. http://dx.doi.org/10.1016/j.schres.2007.12.411.
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Bey, Lionel, Enas Areiqat, Andrea Sano und Marc T. Hamilton. „Reduced lipoprotein lipase activity in postural skeletal muscle during aging“. Journal of Applied Physiology 91, Nr. 2 (01.08.2001): 687–92. http://dx.doi.org/10.1152/jappl.2001.91.2.687.
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Lipoprotein lipase (LPL) is a key enzyme for fatty acid and lipoprotein metabolism in muscle. However, the effect of aging on LPL regulation in skeletal muscle is unknown. We report the effect of aging on LPL regulation in the soleus (red oxidative postural) muscle and the tibialis anterior (white glycolytic non-weight-bearing) muscle in 4- and 24-mo-old Fischer 344 rats and 18- and 31-mo-old Fischer 344 × Brown-Norway F1 (F-344 × BN F1) rats. Total and heparin-releasable LPL (HR-LPL) activities were decreased 38% ( P< 0.01) and 52% ( P < 0.05), respectively, in the soleus muscle of the older Fischer 344 rats. There was a 32% reduction ( P < 0.05) of total LPL protein mass in the soleus muscle with aging. The results were confirmed in another strain. A decrease of total LPL activity (−50%, P < 0.05) was also found in the soleus muscle between 18- and 31-mo-old F-344 × BN F1 rats. LPL mRNA concentration in the soleus muscle was not different between ages. Total LPL protein mass was reduced by 46% ( P < 0.05) in the soleus muscle of the 31-mo-old F-344 × BN F1 rats. In the tibialis anterior muscle, neither LPL activity nor mRNA concentration was affected by age in either strain. In conclusion, LPL regulation in a non-weight-bearing muscle was not affected by aging. However, there was a pronounced reduction in LPL activity and LPL protein mass in postural muscle with aging.
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Milliman, Scott R., A. P. Grima und Carl J. Walters. „Policy Making within an Adaptive Management Framework, with an Application to Lake Trout (Salvelinus namaycush) Management“. Canadian Journal of Fisheries and Aquatic Sciences 44, S2 (19.12.1987): s425—s430. http://dx.doi.org/10.1139/f87-344.
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Using lake trout (Salvelinus namaycush) rehabilitation in the Laurentian Great Lakes as an example, we combine a policy design process known as "adaptive management" in biological circles with basic concepts found in natural resource economics. Emerging from this synthesis of biological and economic thought is a practical method for making policy choice in fisheries in the presence of biological uncertainty. We introduce this method by first reviewing key biotic uncertainties which impede the progress of lake trout rehabilitation. Drawing upon these uncertainties, a framework is proposed for developing a set of policy options. Included in these options are "actively adaptive" policies which are purposely experimental in hopes of both reviving the lake trout fishery and concurrently yielding data which may alleviate the nagging uncertainties. Using basic concepts from natural resource economics, we then outline how, in the presence of the key uncertainties, the policy which most likely maximizes socioeconomic gains can be chosen from the various options. We conclude with some brief policy implications for lake trout rehabilitation.
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Dongarwar, Deepa, Anjali Aggarwal, Kenneth Barning und Hamisu Mohammed Salihu. „Trends in Stillbirths and Stillbirth Phenotypes in the United States: An Analysis of 131.5 Million Births“. International Journal of Maternal and Child Health and AIDS (IJMA) 9, Nr. 1 (10.02.2020): 146–48. http://dx.doi.org/10.21106/ijma.344.
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We examined the trends in stillbirth across gestational age in the United States (US).We conducted a trend analysis using the U.S. Natality and Fetal Death datasets covering 1982 and 2017. We compared the incidence and rates of stillbirth for term, all preterm, moderate-to-late preterm, very preterm, and extreme preterm phenotypes. The incidence of stillbirth decreased for the entire birth cohort over the 36-year period. The rates of overall, term, all preterm, very preterm and moderate-to-late preterm stillbirth decreased from 1982 to 2017; however, the rates for extreme preterm stillbirth increased by about 7.6% over the same study period.
Key words: • Trends in stillbirth • Stillbirth phenotypes • Stillbirth in US
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Bernardo, Monica, Fatemeh Homayounieh, Maria Cristina Rodel Cuter, Luiz Mário Bellegard, Homero Medeiros Oliveira Junior, Gabriela Oliveira Buril, Juliana Santana de Melo Tapajós et al. „CHEST CT USAGE IN COVID-19 PNEUMONIA: MULTICENTER STUDY ON RADIATION DOSES AND DIAGNOSTIC QUALITY IN BRAZIL“. Radiation Protection Dosimetry 197, Nr. 3-4 (Dezember 2021): 135–45. http://dx.doi.org/10.1093/rpd/ncab171.
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Abstract We assessed variations in chest CT usage, radiation dose and image quality in COVID-19 pneumonia. Our study included all chest CT exams performed in 533 patients from 6 healthcare sites from Brazil. We recorded patients’ age, gender and body weight and the information number of CT exams per patient, scan parameters and radiation doses (volume CT dose index—CTDIvol and dose length product—DLP). Six radiologists assessed all chest CT exams for the type of pulmonary findings and classified CT appearance of COVID-19 pneumonia as typical, indeterminate, atypical or negative. In addition, each CT was assessed for diagnostic quality (optimal or suboptimal) and presence of artefacts. Artefacts were frequent (367/841), often related to respiratory motion (344/367 chest CT exams with artefacts) and resulted in suboptimal evaluation in mid-to-lower lungs (176/344) or the entire lung (31/344). There were substantial differences in CT usage, patient weight, CTDIvol and DLP across the participating sites.
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Piatti, Andrés E. „Globular Cluster Candidates in the Sagittarius Dwarf Galaxy“. Astronomical Journal 162, Nr. 6 (24.11.2021): 261. http://dx.doi.org/10.3847/1538-3881/ac2833.
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Abstract Recently, new Sagittarius (Sgr) dwarf-galaxy globular clusters were discovered, which opens the question of the actual size of the Sgr globular cluster population, and therefore on our understanding of the Sgr galaxy formation and accretion history of the Milky Way. Based on Gaia EDR3 and SDSS IV DR16 (APOGEE-2) data sets, we performed an analysis of the color–magnitude diagrams (CMDs) of the eight new Sgr globular clusters found by Minniti et al. from a sound cleaning of the contamination of Milky Way and Sgr field stars, complemented by available kinematic and metal abundance information. The cleaned CMDs and spatial stellar distibutions reveal the presence of stars with a wide range of cluster membership probabilities. Minni 332 turned out to be a younger (<9 Gyr) and more metal-rich ([M/H] ≳ −1.0 dex) globular cluster than M54, the nuclear Sgr globular cluster; as could also be the case of Minni 342, 348, and 349, although their results are less convincing. Minni 341 could be an open cluster candidate (age < 1 Gyr, [M/H] ∼ −0.3 dex), while the analyses of Minni 335, 343, and 344 did not allow us to confirm their physical reality. We also built the Sgr cluster frequency (CF) using available ages of the Sgr globular clusters and compared it with that obtained from the Sgr star formation history. Both CFs are in excellent agreement. However, the addition of eight new globular clusters with ages and metallicities distributed according to the Sgr age–metallicity relationship turns out in a remarkably different CF.
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Hege Hurrish, Katie, Yongwei Su, Sandra Wiley, Zhanjun Hou, Jenna Carter, Hasini Kalpage, Maik Hüttemann et al. „A Novel Isoflavone, ME-344, Enhances Venetoclax Antileukemic Activity Against AML Via Suppression of Oxidative Phosphorylation and Purine Biosynthesis“. Blood 138, Supplement 1 (05.11.2021): 2238. http://dx.doi.org/10.1182/blood-2021-147004.
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Abstract The 5-year survival rate for adult patients with acute myeloid leukemia (AML) treated with cytarabine-based chemotherapy remains less than 30%, due to drug resistance and disease relapse. Recently, a selective inhibitor of anti-apoptotic Bcl-2, venetoclax, was approved by the FDA in combination with low dose cytarabine or hypomethylating agents for treating newly diagnosed AML patients who are 75 years of age or older or for those who are unfit for standard chemotherapy, providing more treatment options for this group of patients. Although the response rate to these newly approved combination therapies is reported to be 70%, the median overall survival is only 10-18 months showing that the duration of response is limited. Therefore, novel therapeutic agents are in demand to enhance venetoclax activity against AML and to combat AML resistant to cytarabine-based chemotherapy. Cytarabine-resistant AML cells lead to relapse and rely on oxidative phosphorylation (OXPHOS) for survival. In addition, it has been reported that targeting OXPHOS can enhance venetoclax activity against preclinical models of AML. Thus, we hypothesize that OXPHOS suppressing agents would be good candidates to combine with and enhance venetoclax antileukemic activity against newly diagnosed AML and those with resistance to cytarabine. A novel isoflavone, ME-344, has been shown to suppress OXPHOS in cell lines derived from solid tumors by inhibiting Complex I of the electron transport chain. We hypothesized that combining ME-344 with venetoclax would result in synergistic antileukemic activity against AML. Consistent with our hypothesis, combining ME-344 with venetoclax resulted in synergistic induction of apoptosis in AML cell lines, including those with acquired cytarabine resistance. The combination of these two agents also resulted in synergistic antileukemic activity in one primary AML patient sample, as determined by MTT assay. The combination of ME-344 and venetoclax prolonged the median survival of MV4-11 leukemia- bearing NSGS mice by 37% (median survival of 48 days compared to 35 days for vehicle control treated mice, n=5 per arm, p<0.0001). This is in contrast to the venetoclax combination with cytarabine, which prolonged median survival of the same xenograft model by 7.5% (Luedtke et al., Signal Transduction and Targeted Therapy, 2020; 5:17). ME-344 alone (9-hour treatment) reduced basal mitochondrial respiration in AML cells by 10% prior to induction of apoptosis. When treated with ME-344 for 8-hours followed by combined ME-344 and venetoclax for an additional 1-hour, basal mitochondrial respiration was reduced by 18% (again prior to detection of apoptosis initiation). This sequential combination regimen also decreased the mitochondrial membrane potential (by JC-1 staining and flow cytometry analysis) when compared to untreated control and single treatment. Additionally, apoptosis induction by the combination of ME-344 and venetoclax or ME-344 alone was significantly enhanced when AML cells were forced to utilize OXPHOS by replacing glucose with galactose in the culture medium. Further investigation revealed that apoptosis induced by ME-344 was partially attenuated when Mcl-1 was overexpressed, Bak was knocked down, or caspase activation was inhibited. This suggests a mechanism that involves components of the intrinsic apoptosis pathway. Targeted metabolomics analyses of MV4-11 cells treated with ME-344 for 8 h revealed a significant reduction of essential metabolites involved in the de novo purine biosynthesis pathway, specifically AICAR (p=0.001) and IMP (p=0.004). Given the critical role of purine in cell proliferation and survival, suppression of purine biosynthesis by ME-344 may represent a novel mechanism underlying its enhancement on the antileukemic activity of venetoclax against AML. Interestingly, inhibition of this pathway by the purine biosynthesis inhibitor lometrexol, also synergistically enhanced apoptosis in AML cells induced by venetoclax. Taken together, these results suggest that ME-344 suppresses OXPHOS and the purine biosynthesis pathway to enhance the antileukemic activity of venetoclax against AML. Further in-depth mechanistic studies into the suppression of purine biosynthesis and OXPHOS, as well as studies of ME-344 and venetoclax against cytarabine-resistant AML in a mouse model are warranted. Disclosures Wiley: MEIPharma: Current Employment.
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Gao, Xiaolong, und Tzyh-Chang Hwang. „Localizing a gate in CFTR“. Proceedings of the National Academy of Sciences 112, Nr. 8 (09.02.2015): 2461–66. http://dx.doi.org/10.1073/pnas.1420676112.
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Experimental and computational studies have painted a picture of the chloride permeation pathway in cystic fibrosis transmembrane conductance regulator (CFTR) as a short narrow tunnel flanked by wider inner and outer vestibules. Although these studies also identified a number of transmembrane segments (TMs) as pore-lining, the exact location of CFTR’s gate(s) remains unknown. Here, using a channel-permeant probe, [Au(CN)2]−, we provide evidence that CFTR bears a gate that coincides with the predicted narrow section of the pore defined as residues 338–341 in TM6. Specifically, cysteines introduced cytoplasmic to the narrow region (i.e., positions 344 in TM6 and 1148 in TM12) can be modified by intracellular [Au(CN)2]− in both open and closed states, corroborating the conclusion that the internal vestibule does not harbor a gate. However, cysteines engineered to positions external to the presumed narrow region (e.g., 334, 335, and 337 in TM6) are all nonreactive toward cytoplasmic [Au(CN)2]− in the absence of ATP, whereas they can be better accessed by extracellular [Au(CN)2]− when the open probability is markedly reduced by introducing a second mutation, G1349D. As [Au(CN)2]− and chloride ions share the same permeation pathway, these results imply a gate is situated between amino acid residues 337 and 344 along TM6, encompassing the very segment that may also serve as the selectivity filter for CFTR. The unique position of a gate in the middle of the ion translocation pathway diverges from those seen in ATP-binding cassette (ABC) transporters and thus distinguishes CFTR from other members of the ABC transporter family.
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Xavier, Lylian Ellen Militão dos Santos, Thays Cristhyna Guimaraes Reis, Amylly Sanuelly da Paz Martins, Juliana Célia de Farias Santos, Nassib Bezerra Bueno, Marília Oliveira Fonseca Goulart und Fabiana Andréa Moura. „Antioxidant Therapy in Inflammatory Bowel Diseases: How Far Have We Come and How Close Are We?“ Antioxidants 13, Nr. 11 (08.11.2024): 1369. http://dx.doi.org/10.3390/antiox13111369.
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Inflammatory bowel diseases (IBD) pose a growing public health challenge with unclear etiology and limited efficacy of traditional pharmacological treatments. Alternative therapies, particularly antioxidants, have gained scientific interest. This systematic review analyzed studies from MEDLINE, Cochrane, Web of Science, EMBASE, and Scopus using keywords like “Inflammatory Bowel Diseases” and “Antioxidants.” Initially, 925 publications were identified, and after applying inclusion/exclusion criteria—covering studies from July 2015 to June 2024 using murine models or clinical trials in humans and evaluating natural or synthetic substances affecting oxidative stress markers—368 articles were included. This comprised 344 animal studies and 24 human studies. The most investigated antioxidants were polyphenols and active compounds from medicinal plants (n = 242; 70.3%). The review found a strong link between oxidative stress and inflammation in IBD, especially in studies on nuclear factor kappa B and nuclear factor erythroid 2-related factor 2 pathways. However, it remains unclear whether inflammation or oxidative stress occurs first in IBD. Lipid peroxidation was the most studied oxidative damage, followed by DNA damage. Protein damage was rarely investigated. The relationship between antioxidants and the gut microbiota was examined in 103 animal studies. Human studies evaluating oxidative stress markers were scarce, reflecting a major research gap in IBD treatment. PROSPERO registration: CDR42022335357 and CRD42022304540.
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Brunsdon, Alfred Richard. „WHAT CAN WE LEARN FROM A NARRATIVE REINTERPRETATION OF A MISSION (HI)STORY? REFLECTING ON THE MISSION HISTORY OF THE DUTCH REFORMED CHURCH ACCORDING TO WILLEM SAAYMAN“. Studia Historiae Ecclesiasticae 41, Nr. 2 (18.12.2015): 100–115. http://dx.doi.org/10.25159/2412-4265/344.
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On 16 May 2015, the well-known missiologist, Willem Saayman, passed away. In this article, his overview of the Dutch Reformed Church (DRC) mission history, Being Missionary, Being Human (2007), is revisited from the perspective of the narrative theory of White and Epston. This reinterpretation rests on the notion that history and religious traditions are structured as narratives that are open for interpretation and reinterpretation. As Saayman depicted the DRC mission history as a problem-saturated narrative, it is argued that unique outcomes also reside within this problem-saturated narrative, creating the possibility for the re-authoring of a liberated mission narrative. It is suggested that the narrative strategies of externalisation and co-authoring can be instrumental in attaining a mission narrative that is truly human.
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Fogarty, Matthew J., Tanya S. Omar, Wen-Zhi Zhan, Carlos B. Mantilla und Gary C. Sieck. „Phrenic motor neuron loss in aged rats“. Journal of Neurophysiology 119, Nr. 5 (01.05.2018): 1852–62. http://dx.doi.org/10.1152/jn.00868.2017.
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Sarcopenia is the age-related reduction of muscle mass and specific force. In previous studies, we found that sarcopenia of the diaphragm muscle (DIAm) is evident by 24 mo of age in both rats and mice and is associated with selective atrophy of type IIx and IIb muscle fibers and a decrease in maximum specific force. These fiber type-specific effects of sarcopenia resemble those induced by DIAm denervation, leading us to hypothesize that sarcopenia is due to an age-related loss of phrenic motor neurons (PhMNs). To address this hypothesis, we determined the number of PhMNs in young (6 mo old) and old (24 mo old) Fischer 344 rats. Moreover, we determined age-related changes in the size of PhMNs, since larger PhMNs innervate type IIx and IIb DIAm fibers. The PhMN pool was retrogradely labeled and imaged with confocal microscopy to assess the number of PhMNs and the morphometry of PhMN soma and proximal dendrites. In older animals, there were 22% fewer PhMNs, a 19% decrease in somal surface area, and a 21% decrease in dendritic surface area compared with young Fischer 344 rats. The age-associated loss of PhMNs involved predominantly larger PhMNs. These results are consistent with an age-related denervation of larger, more fatigable DIAm motor units, which are required primarily for high-force airway clearance behaviors. NEW & NOTEWORTHY Diaphragm muscle sarcopenia in rodent models is well described in the literature; however, the relationship between sarcopenia and frank phrenic motor neuron (MN) loss is unexplored in these models. We quantify a 22% loss of phrenic MNs in old (24 mo) compared with young (6 mo) Fischer 344 rats. We also report reductions in phrenic MN somal and proximal dendritic morphology that relate to decreased MN heterogeneity in old compared with young Fischer 344 rats.
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Tsvetova, N. S. „BOOK REVIEW: GOLUBKOV M.M. WHY DO WE NEED RUSSIAN LITERATURE?“ Siberian Philological Forum 20, Nr. 3 (30.09.2022): 126–29. http://dx.doi.org/10.25146/2587-7844-2022-20-3-129.
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The author of the review analyzes the monograph by M.M. Golubkov, a well-known expert in Russian literature of the 20th century, Professor, Head of the Department of the Lomonosov Moscow State University. This book falls into three parts. The first deals with the relevance of Russian classics of the 20th century, the reasons for its “expulsion” from university and school literature programs, and the didactic potential that is ignored in the era of the Unified State Examination. The second part is devoted to one of the most urgent problems of modern historical and literary science – the problem of periodization. The third chapter of the monograph is a purely analytical one, which presents rather unexpected “rapprochements” of some key people in the latest Russian prose: Gorky and Solzhenitsyn, Solzhenitsyn and Polyakov, etc. From the point of view of the author of the review, the new book by M.M. Golubkov may be of interest not only to university teachers, but also to school teachers of Russian literature of the 20th and early 21st centuries.
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Hennessey, Kiara K., Aaron R. Williams, Kourosh Afshar und Andrew E. MacNeily. „Duplicate publications: A sample of redundancy in the Journal of“. Canadian Urological Association Journal 6, Nr. 3 (25.02.2013): 177–80. http://dx.doi.org/10.5489/cuaj.344.
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Purpose: Redundant publications occur when authors publish apartial or complete duplicate of data from an existing manuscript. The push for academic advancement in medicine may result in redundant publications that erode the quality of literature. We sampled the extent of redundancy within the Journal of Urology.Methods: Original articles published in the Journal of Urology in2006 were reviewed. MEDLINE was used to identify suspectedduplicate publications by combining the last names of the first,second and last authors with keywords provided by the article.Results were limited to 2004 to 2008. Two investigators reviewed the suspected duplicate publications and classified them as duplicate, probable duplicate and salami-slicing.Results: We screened 723 original articles. Of these originalarticles, 13 (1.8%) had some form of redundancy. One (0.1%)original article had a duplicate article, 5 (0.7%) original articleshad probable duplicates, and 7 (1%) original articles were salamisliced. The proportion of redundant articles published prior to, and following, their 2006 index article was 5/13 (38.5%) and 7/13 (53.8%), respectively. One duplicate (7.7%) was published in the same month as its index.Conclusion: Detection of redundant publications is a laboriousprocess for reviewers and editors. This sampling of the Journal of Urology revealed that the duplication rate in this journal is small, but significant. Further assessment of the urological literature is warranted.
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Maharjan, Shreekrishna, Brahmaraju Mopidevi, Meenakshi Kaul Kaw, Nitin Puri und Ashok Kumar. „Human aldosterone synthase gene polymorphism promotes miRNA binding and regulates gene expression“. Physiological Genomics 46, Nr. 24 (15.12.2014): 860–65. http://dx.doi.org/10.1152/physiolgenomics.00084.2014.
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Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke, and renal failure. Like other complex diseases, hypertension is caused by a combination of genetic and environmental factors. The renin-angiotensin-aldosterone system plays an important role in the regulation of blood pressure. The octapeptide angiotensin II (ANG II) is one of the most active vasopressor agents and is obtained from the precursor molecule, angiotensinogen, by the combined proteolytic action of renin and angiotensin-converting enzyme. ANG II increases the expression of aldosterone synthase (coded by Cyp11B2 gene), which is the rate-limiting enzyme in the biosynthesis of aldosterone. Previous studies have shown that increased expression of aldosterone synthase increases blood pressure and cardiac hypertrophy in transgenic mice. Human Cyp11B2 gene has a T/C polymorphism at −344 positions in its 5′-untranslated region (UTR), and the −344T allele is associated with hypertension. Human Cyp11B2 gene also has an A/G polymorphism at 735 position in its 3′-UTR (rs28491316) that is in linkage disequilibrium with single nucleotide polymorphism at −344. We show here that 1) microRNA (miR)-766 binds to the 735G-allele and not the 735A-allele of the hCyp11B2 gene and 2) transfection of miR-766 reduces the human aldosterone synthase mRNA and protein level in human adrenocortical cells H295R. These studies suggest that miR-766 may downregulate the expression of human aldosterone synthase gene and reduce blood pressure in human subjects containing −344T allele.
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Colwell, Mark A., und Lewis W. Oring. „Wing fluttering display by incubating male Wilson's phalaropes“. Canadian Journal of Zoology 66, Nr. 10 (01.10.1988): 2315–17. http://dx.doi.org/10.1139/z88-344.
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Wilson's phalarope (Phalaropus tricolor) exhibits extreme sex-role reversal. Males provide nearly exclusive parental care for eggs and chicks, whereas females compete directly for mates in scramble competition. Males on incubation recess are often harassed by unpaired females. Males flying to nests to resume incubation performed a distinctive flight display when followed by females. Conversely, unaccompanied males returning to nests rarely performed the display. We hypothesize that this display signals to females a male's unavailability as a prospective mate.
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van Winkel, Claudia A., Xiaoyu Fan, Danique Giesen, Glenn Gauderat, Lucia Pattarini, Thomas Jaquin, Anissa Barakat et al. „Abstract 3579: Assessment of target-mediated biodistribution of an 89Zr labeled PD-L1/4-1BB bispecific Mabcalin protein“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 3579. http://dx.doi.org/10.1158/1538-7445.am2023-3579.
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Abstract Background: PRS-344/S095012 is a novel 4-1BB (CD137) and programmed death-ligand 1 (PD-L1) bispecific antibody-Anticalin® fusion protein (MabcalinTM protein) designed to cluster 4-1BB on activated T cells exclusively in the presence of PD-L1 expressing cells. We aimed to study PRS-344/S095012 in vivo biodistribution and pharmacokinetics with 89Zr-positron emission tomography (PET) at a dose with antitumoral activity in mice and evaluate the contribution of each targeting arm. Methods: PRS-344/S095012 lacks cross-reactivity to murine 4-1BB and PD-L1. To explore the PRS-344/S095012 biodistribution in a humanized 4-1BB knock-in mouse model, we synthesized the surrogate 89Zr-Atezo-J10 with the same 4-1BB building block and cross-reactivity to murine PD-L1. Humanized 4-1BB knock-in C57BL/6J (h4-1BB KI B6) and C57BL/6J (B6) mice (n=4-6 per group) were subcutaneously engrafted with murine wildtype MC38 colon adenocarcinoma cells. Tumors were grown to a minimum of ≥50 mm3 (average 163 mm3) before tracer injection. Mice received intravenously 30 µg (2.5 MBq) of 89Zr-PRS-344/S095012 or 89Zr-Atezo-J10 supplemented with PRS-344/S095012 or Atezo-J10 up to 10 mg/kg. Four mice groups were formed to distinguish between bispecific (Atezo-J10 in h4-1BB KI B6), monospecific PD-L1 (Atezo-J10 in B6), monospecific 4-1BB (PRS-344/S095012 in h4-1BB KI B6), and isotype (PRS-344/S095012 in B6) binding up to 4 days post-injection (pi). In addition, a fifth group (5 MBq 89Zr-Atezo-J10) was studied to visualize the bispecific biodistribution up to 7 days pi. At days 1, 2, 4, or 2, 4, 7 pi, mice underwent serial PET imaging to obtain mean and maximum standardized uptake (SUVmean/max) and retro-orbital blood sampling, followed by ex vivo biodistribution. Results: PET imaging showed 89Zr-Atezo-J10 specific tumor accumulation with higher tumor-to-blood ratios of respectively 2.2-, 2.6-, and 2.4-fold (p<0.01) at 4 days pi compared to monospecific binding of PD-L1, 4-1BB, and isotype. The ex vivo biodistribution demonstrated the same trend with respectively 4.2-, 5.5-, and 6.8-fold (p<0.01) increase in tumor-to-blood uptake for 89Zr-Atezo-J10 versus monospecific binding of PD-L1, 4-1BB, and isotype 89Zr-Atezo-J10 spleen uptake was comparable (ns) with monospecific binding of PD-L1 but elevated (p<0.01) compared to 4-1BB or isotype distribution. The uptake in lymph nodes (axillary, cervical, tumor-draining, and mesenteric) did not differ between the groups. Conclusion: 89Zr-Atezo-J10 specific accumulation in PD-L1 expressing tumors is due to both PD-L1 and 4-1BB binding and is higher than with PD-L1 and 4-1BB mono-targeting. This preclinical study supports the clinical evaluation of 89Zr-PRS-344/S095012’s whole-body distribution and the development of tumor-specific 4-1BB targeting bispecifics. Citation Format: Claudia A. van Winkel, Xiaoyu Fan, Danique Giesen, Glenn Gauderat, Lucia Pattarini, Thomas Jaquin, Anissa Barakat, Anne-Marie De La Bigne, Marleen Richter, Nicole Andersen, Julie Legrand, Helene Lelièvre, Elisabeth G. de Vries, Aizea Morales-Kastresana, Marjolijn N. Lub- de Hooge. Assessment of target-mediated biodistribution of an 89Zr labeled PD-L1/4-1BB bispecific Mabcalin protein. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3579.
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Hurrish, Katie H., Yongwei Su, Shraddha Patel, Sandra E. Wiley, Zhanjun Hou, Jenna Carter, Hasini Kalpage et al. „Abstract 3785: ME-344, a novel isoflavone mitochondrial inhibitor, in combination with venetoclax constitutes a new metabolism-targeted approach to overcome resistance to Bcl-2 inhibition and standard of care treatment in AML“. Cancer Research 82, Nr. 12_Supplement (15.06.2022): 3785. http://dx.doi.org/10.1158/1538-7445.am2022-3785.
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Abstract Acute myeloid Leukemia (AML) is an aggressive hematologic malignancy with poor prognosis. Despite chromosomal and genetic heterogeneity, AML are uniformly characterized by increased reliance on oxidative phosphorylation (OXPHOS). This key metabolic hallmark of leukemia was recently reported as a feature of resistance to Cytarabine (AraC)-based therapy. Also, an aggressive phenotype and poor response to chemotherapy is associated with increased levels of Bcl-2. Despite the introduction of the Bcl-2 inhibitor venetoclax (VEN), the overall survival, particularly in older patients, remains poor. Thus, approaches to improve the sensitivity of leukemic cells to AraC-based or Bcl-2 based therapies are urgently needed.Here, we investigated the preclinical activity of ME-344, a novel isoflavone OXPHOS inhibitor, on AML cell lines and relapsed/refractory (R/R) patient samples in vitro and examined the efficacy of ME-344 in combination with VEN in Ara-C sensitive and resistant AML cell lines and patient-derived xenografts (PDX) both in vitro and in vivo.ME-344 (0-300 nM, 24 hr) significantly reduced viability of AML cell lines with EC50 of 75-100 nM and R/R AML patient samples with EC50 of 200-300 nM respectively. The cytotoxic response in AML was enhanced when ME-344 was combined with VEN, producing strong synergistic viability reduction and induction of apoptosis, as evidenced by Annexin V assay and an increased level of cleaved caspase 3 and PARP (immunoblotting). The dual inhibition of OXPHOS/Bcl-2 reduced Mcl-1 levels and showed efficacy in Mcl-1 overexpressingand Ara-C resistant AML models.Functional metabolic characterization of AML by transcriptomics and mass spectrometry demonstrated that ME-344 effectively inhibited biosynthetic pathways of nucleotides uncovering the purine biosynthesis pathway as crucial for therapeutic efficacy. ME-344 induced a dose-dependent decrease in the oxygen consumption rate (by Seahorse assay), in both AraC-sensitive and -resistant AML cell lines, and in R/R AML patient samples, which was further significantly potentiated by combination with VEN.Finally, in an aggressive AML xenograft model, ME-344 (200 mpk, i.v.) combined with subtherapeutic doses of VEN (25 mpk) reduced circulating leukemia burden and extended survival. Ongoing in vivo studies in AML PDX models will address the impact of ME-344 in the context of acquired AraC- and Bcl-2- resistance. In summary, our findings indicate ME-344 alone or in combination with Bcl-2 inhibition constitutes an important therapeutic modality that targets a unique metabolic vulnerability of AML. Citation Format: Katie H. Hurrish, Yongwei Su, Shraddha Patel, Sandra E. Wiley, Zhanjun Hou, Jenna Carter, Hasini Kalpage, Maik Hüttemann, Connie Weng, Holly Edwards, Lisa Polin, Jing Li, Jay Yang, Larry H. Matherly, Sergej Naumovich Konoplev, Jeffrey W. Taub, Marina Konopleva, Yubin Ge, Natalia Baran. ME-344, a novel isoflavone mitochondrial inhibitor, in combination with venetoclax constitutes a new metabolism-targeted approach to overcome resistance to Bcl-2 inhibition and standard of care treatment in AML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3785.
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LANCASTER, David E., Luke A. McNEILL, Michael A. McDONOUGH, Robin T. APLIN, Kirsty S. HEWITSON, Christopher W. PUGH, Peter J. RATCLIFFE und Christopher J. SCHOFIELD. „Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity“. Biochemical Journal 383, Nr. 3 (26.10.2004): 429–37. http://dx.doi.org/10.1042/bj20040735.
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HIF (hypoxia-inducible factor) is an αβ transcription factor that modulates the hypoxic response in many animals. The cellular abundance and activity of HIF-α are regulated by its post-translational hydroxylation. The hydroxylation of HIF is catalysed by PHD (prolyl hydroxylase domain) enzymes and FIH (factorinhibiting HIF), all of which are 2-oxoglutarate- and Fe(II)-dependent dioxygenases. FIH hydroxylates a conserved asparagine residue in HIF-α (Asn-803), which blocks the binding of HIF to the transcriptional co-activator p300, preventing transcription of hypoxia-regulated genes under normoxic conditions. In the present paper, we report studies on possible mechanisms for the regulation of FIH activity. Recently solved crystal structures of FIH indicate that it is homodimeric. Site-directed mutants of FIH at residues Leu-340 and Ile-344, designed to disrupt dimerization, were generated in order to examine the importance of the dimeric state in determining FIH activity. A single point mutant, L340R (Leu-340→Arg), was shown to be predominantly monomeric and to have lost catalytic activity as measured by assays monitoring 2-oxoglutarate turnover and asparagine hydroxylation. In contrast, the I344R (Ile-344→Arg) mutant was predominantly dimeric and catalytically active. The results imply that the homodimeric form of FIH is required for productive substrate binding. The structural data also revealed a hydrophobic interaction formed between FIH and a conserved leucine residue (Leu-795) on the HIF substrate, which is close to the dimer interface. A recent report has revealed that phosphorylation of Thr-796, which is adjacent to Leu-795, enhances the transcriptional response in hypoxia. Consistent with this, we show that phosphorylation of Thr-796 prevents the hydroxylation of Asn-803 by FIH.
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Rubio, Carlos A. „Traditional serrated adenomas and serrated carcinomas in carcinogen-treated rats“. Journal of Clinical Pathology 70, Nr. 4 (26.08.2016): 301–7. http://dx.doi.org/10.1136/jclinpath-2016-204037.
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AimsA recent review of archived sections from early experiments in rats showed neoplasias exhibiting serrated configurations. The aim was to assess the frequency of serrated neoplasias in the colon and small intestine of carcinogen-treated rats.MethodsWhile reviewing archival sections from early experiments in Sprague-Dawley (SD) and Fisher-344 (F-344) rats, we recently detected colonic and intestinal traditional serrated adenomas (displaying serrated or microtubular patterns) and serrated carcinomas. SD rats were injected 1,2-dimethylhydrazine (DMH) for 27 weeks whereas F-344 rats were fed with a pyrolysate (GLU-1) for 24 months. Filed sections from 358 colonic and small intestinal neoplasias were re-evaluated.ResultsDMH-treated SD rats had 215 colonic neoplasias (1.4% were serrated adenomas, 7.9% microtubular adenomas, 2.8% serrated carcinomas and 2.8% microtubular carcinomas). GLU1-treated F-344 rats had 53 colonic neoplasias (1.9% were serrated adenomas and 20.8% microtubular adenomas), and 89 small intestinal neoplasias (1.1% were serrated adenomas, 42.7% microtubular adenomas and 6.7%, microtubular carcinomas).ConclusionsDMH/SD-rats develop serrated and microtubular adenomas and carcinomas in the colon, whereas GLU1/F-344 rats develop microtubular adenomas in the colon and microtubular adenomas and carcinomas in the small intestine. The two rat-settings emerge as suitable models to study the molecular attributes of serrated and microtubular neoplasias under the standard conditions of the laboratory. This study is the first showing that a substantial number of serrated and particularly microtubular adenomas and carcinomas develop in the colon and small intestine of experimental rats. Importantly, serrated and microtubular neoplasias in rats recreate the histology of duodenal and colonic traditional serrated neoplasias in human beings.
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Bonnet, Pierre, Mathilde Bonnefond und Anne Kösem. „What is a Rhythm for the Brain? The Impact of Contextual Temporal Variability on Auditory Perception“. Journal of Cognition 7, Nr. 1 (17.01.2024): 15. http://dx.doi.org/10.5334/joc.344.
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Temporal predictions can be formed and impact perception when sensory timing is fully predictable: for instance, the discrimination of a target sound is enhanced if it is presented on the beat of an isochronous rhythm. However, natural sensory stimuli, like speech or music, are not entirely predictable, but still possess statistical temporal regularities. We investigated whether temporal expectations can be formed in non-fully predictable contexts, and how the temporal variability of sensory contexts affects auditory perception. Specifically, we asked how “rhythmic” an auditory stimulation needs to be in order to observe temporal predictions effects on auditory discrimination performances. In this behavioral auditory oddball experiment, participants listened to auditory sound sequences where the temporal interval between each sound was drawn from gaussian distributions with distinct standard deviations. Participants were asked to discriminate sounds with a deviant pitch in the sequences. Auditory discrimination performances, as measured with deviant sound discrimination accuracy and response times, progressively declined as the temporal variability of the sound sequence increased. Moreover, both global and local temporal statistics impacted auditory perception, suggesting that temporal statistics are promptly integrated to optimize perception. Altogether, these results suggests that temporal predictions can be set up quickly based on the temporal statistics of past sensory events and are robust to a certain amount of temporal variability. Therefore, temporal predictions can be built on sensory stimulations that are not purely periodic nor temporally deterministic.
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Dixon, Susan M., und Robert L. Baker. „Effects of fish on feeding and growth of larval Ischnura verticalis (Coenagrionidae: Odonata)“. Canadian Journal of Zoology 65, Nr. 9 (01.09.1987): 2276–79. http://dx.doi.org/10.1139/z87-344.
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We used laboratory studies to investigate how fish affected a larval zygopteran's activity, ability to locate a food patch, and growth. Larval Ischnura verticalis spent less time at food patches in the presence of fish (Lepomis gibbosus) when food patches were permanent, but when food patches were ephemeral, fish did not have a significant effect. In addition, fish had no effect on larval feeding on mobile prey (Daphnia magna), nor did fish have any effect on growth of larvae supplied with ephemeral prey patches.
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Głowacka, Urszula, Marcin Magierowski, Zbigniew Śliwowski, Jakub Cieszkowski, Małgorzata Szetela, Dagmara Wójcik-Grzybek, Anna Chmura, Tomasz Brzozowski, John L. Wallace und Katarzyna Magierowska. „Hydrogen Sulfide-Releasing Indomethacin-Derivative (ATB-344) Prevents the Development of Oxidative Gastric Mucosal Injuries“. Antioxidants 12, Nr. 8 (02.08.2023): 1545. http://dx.doi.org/10.3390/antiox12081545.
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Hydrogen sulfide (H2S) emerged recently as an anti-oxidative signaling molecule that contributes to gastrointestinal (GI) mucosal defense and repair. Indomethacin belongs to the class of non-steroidal anti-inflammatory drugs (NSAIDs) and is used as an effective intervention in the treatment of gout- or osteoarthritis-related inflammation. However, its clinical use is strongly limited since indomethacin inhibits gastric mucosal prostaglandin (PG) biosynthesis, predisposing to or even inducing ulcerogenesis. The H2S moiety was shown to decrease the GI toxicity of some NSAIDs. However, the GI safety and anti-oxidative effect of a novel H2S-releasing indomethacin derivative (ATB-344) remain unexplored. Thus, we aimed here to compare the impact of ATB-344 and classic indomethacin on gastric mucosal integrity and their ability to counteract the development of oxidative gastric mucosal injuries. Wistar rats were pretreated intragastrically (i.g.) with vehicle, ATB-344 (7–28 mg/kg i.g.), or indomethacin (5–20 mg/kg i.g.). Next, animals were exposed to microsurgical gastric ischemia-reperfusion (I/R). Gastric damage was assessed micro- and macroscopically. The volatile H2S level was assessed in the gastric mucosa using the modified methylene blue method. Serum and gastric mucosal PGE2 and 8-hydroxyguanozine (8-OHG) concentrations were evaluated by ELISA. Molecular alterations for gastric mucosal barrier-specific targets such as cyclooxygenase-1 (COX)-1, COX-2, heme oxygenase-1 (HMOX)-1, HMOX-2, superoxide dismutase-1 (SOD)-1, SOD-2, hypoxia inducible factor (HIF)-1α, xanthine oxidase (XDH), suppressor of cytokine signaling 3 (SOCS3), CCAAT enhancer binding protein (C/EBP), annexin A1 (ANXA1), interleukin 1 beta (IL-1β), interleukin 1 receptor type I (IL-1R1), interleukin 1 receptor type II (IL-1R2), inducible nitric oxide synthase (iNOS), tumor necrosis factor receptor 2 (TNFR2), or H2S-producing enzymes, cystathionine γ-lyase (CTH), cystathionine β-synthase (CBS), or 3-mercaptopyruvate sulfur transferase (MPST), were assessed at the mRNA level by real-time PCR. ATB-344 (7 mg/kg i.g.) reduced the area of gastric I/R injuries in contrast to an equimolar dose of indomethacin. ATB-344 increased gastric H2S production, did not affect gastric mucosal PGE2 content, prevented RNA oxidation, and maintained or enhanced the expression of oxidation-sensitive HMOX-1 and SOD-2 in line with decreased IL-1β and XDH. We conclude that due to the H2S-releasing ability, i.g., treatment with ATB-344 not only exerts dose-dependent GI safety but even enhances gastric mucosal barrier capacity to counteract acute oxidative injury development when applied at a low dose of 7 mg/kg, in contrast to classic indomethacin. ATB-344 (7 mg/kg) inhibited COX activity on a systemic level but did not affect cytoprotective PGE2 content in the gastric mucosa and, as a result, evoked gastroprotection against oxidative damage.
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Singal, Kiran Kumar, Neerja Singal, Parveen Gupta, Nidhi Jain, Neha Talwar und Yuvraj Singh Cheema. „Ascariasis in the Gall Bladder - A Rare Case“. Bangladesh Journal of Medical Science 13, Nr. 3 (06.06.2014): 343–44. http://dx.doi.org/10.3329/bjms.v13i3.17740.
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Settlement of adult form ascariasis parasite in the gall bladder is rare constituting 2.1 % of hepatobiliary ascariasis4. Radiologic imaging methods play an important role in the diagnosis of the parasite in the biliary tree. Computed tomography (CT), magnetic resonance imaging (MRI) and endoscopic retrograde cholangiopancreatography (ERCP) are used in the diagnosis of hepatobiliary ascariasis. However, ultrasonography is still the first method and most preferred due to its ease of applicability and the fact that it is inexpensive and non-invasive. We report a rare case of Ascariasis lumbricoides present in gall bladder. DOI: http://dx.doi.org/10.3329/bjms.v13i3.17740 Bangladesh Journal of Medical Science Vol.13(3) 2014 p.343-344
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Ramos, Howard. „Assessing the tangible and intangible benefits of tourism: Perceptions of economic, social, and cultural impacts in Labrador’s Battle Harbour Historic District“. Island Studies Journal 11, Nr. 1 (2016): 209–26. http://dx.doi.org/10.24043/isj.344.
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Literature on rural and small island tourism critically questions the commodification of culture and landscapes, showing that replacing rural resource based industries with tourism often leads to a mummification of culture and questionable economic payoffs. Using original survey and qualitative data from three communities surrounding Labrador’s Battle Harbour Historic District, this paper explores how rural and island communities perceive the benefits of tourism and interactions with tourists. The paper finds that residents value the cultural showcasing of their communities and history, but are ambiguous about the economic rewards of tourism. We conclude by questioning whether the cultural rewards of tourism, around meaning making, outweigh other rewards around promoting economically and socially viable communities.
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Smith, John F., Charles Li, Myron Roth und Loren G. Hepler. „Solubility of ammonia in chloroform: analysis in terms of Henry's law and the equilibrium constant for hydrogen-bonded complex formation“. Canadian Journal of Chemistry 67, Nr. 12 (01.12.1989): 2213–17. http://dx.doi.org/10.1139/v89-344.
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We have measured the solubility of ammonia in chloroform at several pressures and at three temperatures (25, 30, and 35 °C). Results of these measurements have been analysed in terms of the Henry's law constant that applies to "simple" dissolution of the type B(g) = B(dissolved) and the equilibrium constant K for the liquid phase complex-forming equilibrium represented by A + B = AB where A and B represent chloroform and ammonia, respectively. As expected on the basis of this analysis, ammonia is more soluble (same pressure and temperature) in chloroform than in carbon tetrachloride, where no hydrogen-bonded complex can be formed. Keywords: gas solubility, hydrogen-bonded complexes, Henry's law constant, ammonia–chloroform complex, chloroform-ammonia complex.
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Zakharevich, A. V. „THE FATE OF THE MARCHING ATAMANS OF THE DON REGIMENTS ON THE CAUCASIAN LINE IN 1801-1816. ACCORDING TO THE LITERATURE AND DOCUMENTS OF THE STATE ARCHIVE OF THE ROSTOV REGION (GARO)“. Vestnik scientific and methodological council in environmental engineering and water management, Nr. 23 (2021): 72–76. http://dx.doi.org/10.26897/2618-8732-2021-23-72-76.
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The article describes the biographies of the Donets marching atamans on the Caucasian line from the very beginning of the war, in the period 1801-1816, which were thoroughly forgotten, although it cannot be said that they did not fall into the field of view of researchers, but they showed different levels of interest in them. According to data from scientific research and from the funds, 341 (Military Chancellery of the Don Army) and 344 (Military Headquarters of the Don Army) GARO sometimes do not coincide with each other. If we proceed from the premise that the archive is a more accurate installation of the truth, then we will try to correct the inaccuracies accumulated in the literature with the help of designated funds.
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Majer-Bobetko, Sanja. „Between music and ideologies: Croatian music criticism from the beginning to World War II“. Muzyka 63, Nr. 4 (31.12.2018): 55–64. http://dx.doi.org/10.36744/m.344.
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As the Croatian lands were exposed to often aggressive Austrian, Hungarian, and Italian politics until WWI and in some regions even later, so Croatian music criticism was written in the Croatian, German and Italian languages. To the best of our knowledge, the history of Croatian music criticism began in 1826 in the literary and entertainment journal Luna, and was written by an anonymous author in the German language.A forum for Croatian language music criticism was opened in Novine Horvatzke, i.e. in its literary supplement Danica horvatska, slavonska i dalmatinska in 1835, which officially started to promote the Croatian National Revival, setting in motion the process of constituting the Croatian nation in the modern sense of the word. However, those articles cannot be considered musical criticism, at least not in the modern sense of the word, as they never went beyond the level of mere journalistic reports. The first music criticism in the Croatian language in the true sense of the word is generally considered a very comprehensive text by a poet Stanko Vraz (1810-51) about a performance of the first Croatian national opera Ljubav i zloba (Love and malice) by Vatroslav Lisinski (1819-54) from 1846. In terms of its criteria for judgement, that criticism proved to become a model for the majority of 19th-century and later Croatian music criticism. Two judgement criteria are clearly expressed within it: national and artistic.Regardless of whether we are dealing with 1) ideological-utilitarian criticism, which was directed towards promoting the national ideology (Franjo Ksaver Kuhač, 1834-1911; Antun Dobronić, 1878-1955), 2) impressionist criticism based on the critic’s subjective approach to particular work (Antun Gustav Matoš, 1873-1914; Milutin Cihlar Nehajev, 1880-1931; Nikola Polić, 1890-1960), or 3) Marxist criticism (Pavao Markovac, 1903-41), we may observe the above mentioned two basic criteria. Only at the end of the period under consideration the composer Milo Cipra (1906-85) focused his interest on immanent artistic values, shunning any ideological utilitarianism, and insisting on the highest artistic criteria.
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Lartaud, I., L. Bray-des-Boscs, J. M. Chillon, J. Atkinson und C. Capdeville-Atkinson. „In vivo cerebrovascular reactivity in Wistar and Fischer 344 rat strains during aging“. American Journal of Physiology-Heart and Circulatory Physiology 264, Nr. 3 (01.03.1993): H851—H858. http://dx.doi.org/10.1152/ajpheart.1993.264.3.h851.
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Basal cerebral blood flow (CBF) and CBF regulation after hypercapnia and hypotensive hemorrhage were investigated using H2 clearance in the frontal cortex of awake 2-, 14-, or 23-mo-old Wistar or Fischer 344 rats. Basal CBF decreased in old Wistar but not in mature Wistar (old 64.4 +/- 2.8, mature 87.6 +/- 2.6, young 79.6 +/- 2.2 ml.min-1 x 100 g-1) or in old Fischer 344 (old 71.9 +/- 2.9, young 73.3 +/- 1.6 ml.min-1 x 100 g-1) rats. Cerebrovascular reactivity to hypercapnia decreased in mature and old Wistar (old 2.1 +/- 0.3, mature 3.1 +/- 0.7, young 7.0 +/- 2.1 ml.min-1 x 100 g-1 x mmHg-1) but not in old Fischer 344 rats (old 4.6 +/- 1.4, young 4.9 +/- 0.9 ml.min-1 x 100 g-1 x mmHg-1). The lower limit of CBF autoregulation increased by 20 mmHg during maturation and/or aging in the two strains. Because blood gases and pH evolved similarly in both strains, we postulate that differences in cerebrovascular structure and/or function explain the differences in CBF regulation in the older representatives of the two strains.
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Kowalska, Małgorzata, Marcin Fehlau, Maciej Cymerys und Przemysław Guzik. „A thousand words about running fitness tests“. Journal of Medical Science 88, Nr. 3 (13.03.2019): 184–91. http://dx.doi.org/10.20883/jms.344.
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Running is undertaken for different reasons, including improvement or maintenance of health and fitness. Many tests are employed for the estimation of the fitness in runners. In this review, we describe five field tests (Cooper test, Conconi test, 6-Minute Walk Test, 20-meter Multistage Fitness Test, and Harvard Step Test) and one laboratory cardiopulmonary exercise test (CPET) on a treadmill. A properly selected fitness test may help to estimate or measure the maximal oxygen consumption (VO2), thresholds for the aerobic and anaerobic metabolism, or restitution after the exercise. Such information is used for planning the training process, monitoring the progress of physical fitness or predicting the target distance or speed during competitions. In patients with cardiovascular or pulmonary diseases, this information may help to plan the intensity of daily activity or physical rehabilitation. Testing physical fitness is challenging, however when made appropriately, it delivers valuable physiological and clinical information.
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Cardoso-Saldaña, G., J. Juarez-Rojas, J. Zamora-Gonzalez, M. Raygoza-Perez, R. Martinez-Alvarado, R. Posadas-Romero und C. Posadas-Romero. „We-P13:344 C-reactive protein, their relationships with metabolic syndrome and insulin resistance in Mexican adolescents“. Atherosclerosis Supplements 7, Nr. 3 (Januar 2006): 422. http://dx.doi.org/10.1016/s1567-5688(06)81697-1.
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SHAW, IAN. „Richard Disney, Can We Afford to Grow Older?, The MIT Press, London, 1996, 344 pp., £24.95 hard.“ Journal of Social Policy 26, Nr. 4 (Oktober 1997): 543–70. http://dx.doi.org/10.1017/s004727949735510x.
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Erick, Timothy, Emma Reilly, Jack Wands und Laurent Brossay. „Salivary gland lymphocyte response to murine cytomegalovirus (INC1P.344)“. Journal of Immunology 194, Nr. 1_Supplement (01.05.2015): 54.1. http://dx.doi.org/10.4049/jimmunol.194.supp.54.1.
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Abstract The β-herpes virus MCMV, a homologue of HCMV, is a well-characterized animal model of viral infection that results in a non-replicative, chronic infection of an immune-competent animal. In most organs, MCMV is cleared within days by cytotoxic lymphocytes. However, the virus persists in the submandibular salivary glands (SMG) for several weeks, before establishing latency for the life of the host. NK cells are crucial for the early containment of MCMV before T cells can mount an effector response. Recent work from our laboratory has shown that SMG NK cells are hyporesponsive during MCMV infection. Here we show that SMG NK cells regain normal effector functions against MCMV when adoptively transferred into different tissue environments. This indicates that the hyporesponsive phenotype observed is tissue specific, and not cell-intrinsic. In addition, using E4BP4 deficient animals, we determined that two CD3-NK1.1+ subsets reside within the salivary glands. One subset is derived from the conventional NK cell population and relies on E4BP4 for development, while the other is E4BP4 independent. When the E4BP4 independent NK cells are transferred into different tissue environments, they produce IFN-γ in response to MCMV infection. The SMGs of E4BP4-/- mice also contain a novel population of CD3+NK1.1+NKp46+ cells that produce IFN-γ during MCMV infection. Altogether, our data show that the SMG tissue environment shapes a unique repertoire of NK1.1+ cells with distinctive phenotypes.
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Mückler, Hermann. „Neonbasu, Gregor: We Seek Our Roots. Oral Tradition in Biboki, West Timor“. Anthropos 108, Nr. 1 (2013): 344–46. http://dx.doi.org/10.5771/0257-9774-2013-1-344-1.
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Ray, Andrew D., Toshiyuki Ogasa, Ulysses J. Magalang, John A. Krasney und Gaspar A. Farkas. „Aging increases upper airway collapsibility in Fischer 344 rats“. Journal of Applied Physiology 105, Nr. 5 (November 2008): 1471–76. http://dx.doi.org/10.1152/japplphysiol.00166.2008.
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The upper airway muscles play an important role in maintaining upper airway collapsibility, and the incidence of sleep-disordered breathing increases with age. We hypothesize that the increase in airway collapsibility with increasing age can be linked to changes in upper airway muscle mechanics and structure. Eight young (Y: 6 mo) and eight old (O: 30 mo) Fischer 344 rats were anesthetized and mechanically ventilated, and the pharyngeal pressure associated with flow limitation (Pcrit) was measured 1) with the hypoglossal (cnXII) nerve intact, 2) following bilateral cnXII denervation, and 3) during cnXII stimulation. With the cnXII intact, the upper airways of older rats were more collapsible compared with their younger counterparts [Pcrit = −7.1 ± 0.6 (SE) vs. −9.5 ± 0.7 cmH2O, respectively; P = 0.033]. CnXII denervation resulted in an increase in Pcrit such that Pcrit became similar in both groups (O: −4.2 ± 0.5 cmH2O; Y: −5.4 ± 0.5 cmH2O). In all rats, cnXII stimulation decreased Pcrit (less collapsible) in both groups (O: −11.3 ± 1.0 cmH2O; Y: −10.2 ± 1.0 cmH2O). The myosin heavy chain composition of the genioglossus muscle demonstrated a decrease in the percentage of the IIb isoform (38.3 ± 2.5 vs. 21.7 ± 1.7%; P < 0.001); in contrast, the sternohyoid muscle demonstrated an increase in the percentage of the IIb isoform (72.2 ± 2.5 vs. 58.4 ± 2.3%; P = 0.001) with age. We conclude that the upper airway becomes more collapsible with age and that the increase in upper airway collapsibility with age is likely related to altered neural control rather than to primary alterations in upper airway muscle structure and function.
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Blanchfield, P. J., und M. S. Ridgway. „Reproductive timing and use of redd sites by lake-spawning brook trout (Salvelinus fontinalis)“. Canadian Journal of Fisheries and Aquatic Sciences 54, Nr. 4 (01.04.1997): 747–56. http://dx.doi.org/10.1139/f96-344.
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We provide a detailed description of a salmonine mating system based on daily observations of tagged individuals in a lake-spawning population of brook trout (Salvelinus fontinalis) throughout two breeding seasons. Actual spawning occurred over a period of ~50 d. Over 90% of spawning males were present soon after spawning commenced and outnumbered females for the duration of the spawning period. The amount of time males and females remained on the spawning grounds increased with body size; however, males were present over a longer period than females of equivalent size. A distinct seasonal peak in spawning activity (~15 d) accounted for 58 and 84% (1994 and 1995) of all reproduction and was coincident with a decline in water temperature below 11°C and increased rainfall. Selection of redd sites by female brook trout was determined by groundwater flow which was significantly greater than at nonspawning sites. A preference for certain redd sites was observed, with 50% of spawnings occurring at 11 sites. The construction of multiple redds and duration in spawning activity by females increased with body size. Extensive reuse of redd sites and rapid replacement of females during removal experiments indicate that redd sites are a limiting resource.
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Hawraa Dheyaa Asfoor und Esam A. Al-Nussairy. „Effect of Flow Resistance through a Narrow Catheterized Stenosed Artery: Analytical Study“. Journal of Wasit for Science and Medicine 16, Nr. 1 (28.02.2023): 24–30. http://dx.doi.org/10.31185/jwsm.344.
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In this research, we present an analytical study of the effect of resistance to flow blood through a narrowed artery for catheterization. Vascular diseases are among the most common diseases in countries of the world that can cause cerebral clots or strokes. Where stenosis is the occurrence of abnormal growth on the artery wall, which causes obstruction, in the movement of blood flow, the current model simulates the study of blood flow, given that the blood is Newtonian, incompressible, and steady, with a viscosity and density constant. It was built mathematically to describe the movement of the physiological fluid that represents blood in a gap between two eccentric tubes, where the inner tube is a solid and unified one that represents the moving catheter. While the other is a tapered cylindrical one that represents the artery with overlapping stenosis, where the insertion of the stenosis leads to a change in the blood characteristics (axial velocity, flux and resistance) .The current results showed that the increase in the axial velocity of the stationary catheter is much higher than that of the fixed one, and that the flow resistance increases with the stenosis of the artery.
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Coenen, Eva A., Susana C. Raimondi, Jochen Harbott, Martin Zimmermann, Todd A. Alonzo, Anne Auvrignon, H. Berna Beverloo et al. „Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study“. Blood 117, Nr. 26 (30.06.2011): 7102–11. http://dx.doi.org/10.1182/blood-2010-12-328302.
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Abstract We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P < .001). Trisomy 8, the most frequent specific ACA (n = 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P = .003; Cox model for OS hazard ratio (HR) 0.54, P = .03), on the basis of reduced relapse rate (26% vs 49%, P < .001). Trisomy 19 (n = 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P = .04; OS 24% vs 50%, P < .001; HR 1.77, P = .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P = .01). Complex karyotype, defined as ≥ 3 abnormalities, was present in 26% (n = 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P = .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied.
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Gallegos, Valerie, Florencia Madorsky Rowdo, Jessica White, Hui-Hsuan Kuo, Enrique Podaza, Laura Martin und Olivier Elemento. „344 The Potential Benefits of Using Senolytics in Colorectal Cancer Treatment“. Journal of Clinical and Translational Science 7, s1 (April 2023): 102. http://dx.doi.org/10.1017/cts.2023.388.
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OBJECTIVES/GOALS: Anti-cancer therapies, such as chemotherapy, can induce senescence. Senescent cells may produce factors that can promote tumor progression. In this study, we will investigate the effect of senolytics and anti-cancer treatment on fibroblasts, which are a part of the tumor microenvironment, and patient-derived colorectal cancer organoids. METHODS/STUDY POPULATION: We will induce senescence in fibroblast lines via irradation. Induction of senescence will be confirmed by monitoring SASP production, changes in morphology and proliferation rates, and senescence-associated b-galactosidase activity. To investigate the efficacy of senolytics on senescence-induced fibroblasts and CRC tumor organoids, we will creat a dose response curve and calculate IC50 values for proliferating fibroblast, senescent fibroblasts and CRC organoids. To identify the synergistic effects of anti-cancer and senolytic compounds, including Navitoclax and Dasatinib, on fibroblasts and CRC organoids, we will create dose matrixes using senolytics at concentrations that were shown to have senolytic activity and drugs from an anti-cancer library. RESULTS/ANTICIPATED RESULTS: If senescence is induced in the fibroblast lines, we expect to see no changes in confluency over 4 days, the morphology will change from a thin, spindly shape to a flattened shape, and senescence-associated b-galactosidase activity will be observed. After the fibroblast lines are treated with potential senolytic compounds, we would expect to see decreased viability in the senescence-induced fibroblast lines when compared to proliferating fibroblast lines. We predict that the viability of CRC organoid lines will slightly decrease at high concentrations of the senolytic due to overall toxicity. We expect that the senolytic and anti-cancer compounds will have a synergistic effect. Senolytic activity could reduce the senescent cell population that was developed in response to anti-cancer therapy. DISCUSSION/SIGNIFICANCE: There is an increased interest in identifying compounds that selectively promote apoptosis in senescent cells. This study uses a cell-based approach to validate senolytic activity of compounds with senolytic potential in senescence-induced fibroblast lines and investigates the synergistic effects of senolytics and anti-cancer compounds on CRC.
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Iqbal, Muhammad, Muksalmina Muksalmina, Anhar Nasution, Jummaidi Saputra und Wiratmadinata Wiratmadinata. „APPLICATION OF RESTORATIVE JUSTICE IN TRAFFIC ACCIDENTS CASES“. Proceedings of Malikussaleh International Conference on Law, Legal Studies and Social Science (MICoLLS) 3 (30.12.2023): 0011. http://dx.doi.org/10.29103/micolls.v3i-.344.
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This research aims to explain the efforts and factors that influence the implementation of restorative justice in traffic accident cases at the Banda Aceh Police Traffic Unit. The research results show that the application of restorative justice in resolving traffic accident cases is carried out by investigators after there is peace between the perpetrator and the victim's family. This is done before the Investigator sends a Notification Letter of Commencement of Investigation to the Public Prosecutor so that the case is not continued. Factors that influence the implementation of restorative justice consist of two factors, namely law enforcement and community cultural laws. The law enforcement factor is the lack of knowledge and understanding of investigators regarding applicable laws and regulations. Community legal culture factors are related to religion, values, attitudes and behavior in people's lives so that they influence decision making to resolve traffic accident cases experienced through restorative justice. We hope that traffic accident unit investigators from the Banda Aceh Poresta Traffic Unit can increase their knowledge and understanding of procedures for handling traffic accidents through restorative justice. So that the application of restorative justice in resolving traffic accident cases can be carried out in accordance with the procedures for resolving cases based on the provisions of applicable laws and regulations.
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McDonald, R. B., J. S. Hamilton, J. S. Stern und B. A. Horwitz. „Regional blood flow of exercise-trained younger and older cold-exposed rats“. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 256, Nr. 5 (01.05.1989): R1069—R1075. http://dx.doi.org/10.1152/ajpregu.1989.256.5.r1069.
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O2 consumption (thermogenesis) and regional blood flows (measured using radioactively labeled microspheres) were evaluated in younger (12 mo) and older (24 mo) sedentary and exercised male Fischer 344 (F-344) rats. These variables were measured at rest and during exposure to 6 degrees C. Exercise-trained rats were run on a motor-driven treadmill 5 days/wk, 1 h/day, at 20 m/min for 6 mo. Resting rates of O2 consumption did not differ with age or exercise training. However, thermogenesis during cold exposure was significantly greater in the older exercised rats than in the other three groups. This difference did not reflect a greater contribution from brown fat as indicated by the fact that total blood flow to the brown fat depots during cold exposure was not greater in the older exercised vs. the other rat groups. Neither exercise training nor age had a significant effect on specific resting blood flow (expressed as ml.min-1.g tissue mass-1) to most of the organs measured, including heart, kidney, brown fat, white fat, and skeletal muscle. The notable exception to this was in the spleen of the older sedentary animals where flow was diminished compared with that in the older exercised animals. We conclude that aging, between 12 and 24 mo of age, and/or exercise training have only a minor effect on regional blood flow of F-344 rats during rest or cold exposure and that the enhanced thermogenesis seen in cold-exposed older exercised vs. sedentary F-344 rats cannot be explained by a greater contribution from brown fat.