bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorophore-Conjugated Iron Oxide Nanoparticle Labeling and Analysis of Engrafting Human Hematopoietic Stem Cells
Authors: Maxwell Dustin J. , Bonde Jesper , Hess David A. , Hohm Sarah A. , Lahey Ryan , Zhou Ping , Creer Michael H. , Piwnica-Worms David , Nolta Jan A. 
Published: December 2007

AbstractThe use of nanometer-sized iron oxide particles combined with molecular imaging techniques enables dynamic studies of homing and trafficking of human hematopoietic stem cells (HSC). Identifying clinically applicable strategies for loading nanoparticles into primitive HSC requires strictly defined culture conditions to maintain viability without inducing terminal differentiation. In the current study, fluorescent molecules were covalently linked to dextran-coated iron oxide nanoparticles (Feridex) to characterize human HSC labeling to monitor the engraftment process. Conjugating fluorophores to the dextran coat for fluorescence-activated cell sorting purification eliminated spurious signals from nonsequestered nanoparticle contaminants. A short-term defined incubation strategy was developed that allowed efficient labeling of both quiescent and cycling HSC, with no discernable toxicity in vitro or in vivo. Transplantation of purified primary human cord blood lineage-depleted and CD34+ cells into immunodeficient mice allowed detection of labeled human HSC in the recipient bones. Flow cytometry was used to precisely quantitate the cell populations that had sequestered the nanoparticles and to follow their fate post-transplantation. Flow cytometry endpoint analysis confirmed the presence of nanoparticle-labeled human stem cells in the marrow. The use of fluorophore-labeled iron oxide nanoparticles for fluorescence imaging in combination with flow cytometry allows evaluation of labeling efficiencies and homing capabilities of defined human HSC subsets.Disclosure of potential conflicts of interest is found at the end of this article.
Distinct Effects of the Soluble Versus Membrane-Bound Forms of the Notch Ligand Delta-4 on Human CD34+CD38low Cell Expansion and Differentiation
Authors: Lahmar Medhi , Catelain Cyril , Poirault Sonia , Dorsch Marion , Villeval Jean-Luc , Vainchenker William , Albagli Olivier , Lauret Evelyne 
Published: December 2007

Abstract
Although Notch ligands are considered to activate signaling through direct cell-cell contact, the existence of soluble forms has been demonstrated. However, their roles remain controversial: soluble forms have been reported to mimic the biological activity of membrane-bound form, whereas other studies rather suggested an antagonistic activity toward their full-length counterparts. We previously observed that membrane-bound Delta4-expressing S17 stroma (mbD4/S17) reduced human CD34+CD38low cell proliferation and favored self-renewal. Here, we assessed the effects of a soluble form of Delta4 (solD4) by exposing CD34+CD38low cells to S17 feeders engineered to express solD4 (solD4/S17). In contrast to mbD4/S17, (a) solD4/S17 increased 10-fold cell production after 2 weeks, through enhanced cell proliferation, and (b) it did not preserve colony-forming cell and long-term culture-initiating cell potential of output CD34+ cells. mbD4 and solD4 appeared to also differ in their signaling. Indeed, mbD4, but not solD4, strongly activated both CSL (the nuclear mediator of Notch signaling) in Hela cells overexpressing Notch1 and transcription of some classic Notch target genes in CD34+CD38low cells. Furthermore, both biological effects and CSL activation elicited by mbD4 were strictly dependent upon the γ-secretase complex, whereas solD4 enhanced cell expansion in a partially γ-secretase-independent manner. Altogether, these results suggest that part of solD4 activity did not rely upon canonical Notch pathway.
Disclosure of potential conflicts of interest is found at the end of this article.
Connexin Expression and Functional Analysis of Gap Junctional Communication in Mouse Embryonic Stem Cells
Authors: Wörsdörfer Philipp , Maxeiner Stephan , Markopoulos Christian , Kirfel Gregor , Wulf Volker , Auth Tanja , Urschel Stephanie , von Maltzahn Julia , Willecke Klaus 
Published: December 2007

Abstract
Gap junctional intercellular communication (GJIC) has been suggested to be necessary for cellular proliferation and differentiation. We wanted to investigate the function of GJIC in mouse embryonic stem (ES) cells using pharmacological inhibitors or a genetic approach to inhibit the expression of connexins, that is, the subunit proteins of gap junction channels. For this purpose, we have analyzed all known connexin genes in mouse ES cells but found only three of them, Cx31, Cx43, and Cx45, to be expressed as proteins. We have demonstrated by coimmunoprecipitation that Cx31 and Cx43, as well as Cx43 and Cx45, probably form heteromeric gap junction channels, whereas Cx31 and Cx45 do not. The pharmacological inhibitors reduced GJIC between ES cells to approximately 3% and initiated apoptosis, suggesting an antiapoptotic effect of GJIC. In contrast to these results, reduction of GJIC to approximately 5% by decreased expression of Cx31 or Cx45 via RNA interference in homozygous Cx43-deficient ES cells did not lead to apoptosis. Additional studies suggested that apoptotic death of ES cells and adult stem cells reported in the literature is likely due to a cytotoxic side effect of the inhibitors and not due to a decrease of GJIC. Using the connexin expression pattern in mouse ES cells, as determined in this study, multiple connexin-deficient ES cells can now be genetically engineered in which the level of GJIC is further decreased, to clarify whether the differentiation of ES cells is qualitatively or quantitatively compromised.
Disclosure of potential conflicts of interest is found at the end of this article.
Downregulation of Multiple Stress Defense Mechanisms During Differentiation of Human Embryonic Stem Cells
Authors: Saretzki Gabriele , Walter Theresia , Atkinson Stuart , Passos Jõao F. , Bareth Bettina , Keith W. Nicol , Stewart Rebecca , Hoare Stacey , Stojkovic Miodrag , Armstrong Lyle , von Zglinicki Thomas , Lako Majlinda 
Published: December 2007

Abstract
Evolutionary theory predicts that cellular maintenance, stress defense, and DNA repair mechanisms should be most active in germ line cells, including embryonic stem cells that can differentiate into germ line cells, whereas it would be energetically unfavorable to keep these up in mortal somatic cells. We tested this hypothesis by examining telomere maintenance, oxidative stress generation, and genes involved in antioxidant defense and DNA repair during spontaneous differentiation of two human embryonic stem cell lines. Telomerase activity was quickly downregulated during differentiation, probably due to deacetylation of histones H3 and H4 at the hTERT promoter and deacetylation of histone H3 at hTR promoter. Telomere length decreased accordingly. Mitochondrial superoxide production and cellular levels of reactive oxygen species increased as result of increased mitochondrial biogenesis. The expression of major antioxidant genes was downregulated despite this increased oxidative stress. DNA damage levels increased during differentiation, whereas expression of genes involved in different types of DNA repair decreased. These results confirm earlier data obtained during mouse embryonic stem cell differentiation and are in accordance with evolutionary predictions.
Disclosure of potential conflicts of interest is found at the end of this article.
Cardiopulmonary effects of administration of a combination solution of xylazine, guaifenesin, and ketamine or inhaled isoflurane in mechanically ventilated calves
Authors: Kerr Carolyn L. , Windeyer Claire , Bouré Ludovic P. , Mirakhur Kuldip K. , McDonell Wayne 
Published: December 2007

Abstract
Objective—To compare the cardiopulmonary effects of administration of a solution of xylazine, guaifenesin, and ketamine (XGK) or inhaled isoflurane in mechanically ventilated calves undergoing surgery.
Animals—13 male calves 2 to 26 days of age.
Procedures—In calves in the XGK group, anesthesia was induced (0.5 mL/kg) and maintained (2.5 mL/kg/h) with a combination solution of xylazine (0.1 mg/mL), guaifenesin (50 mg/mL), and ketamine (1.0 mg/mL). For calves in the isoflurane group, anesthesia was induced and maintained with isoflurane in oxygen. The rates of XGK infusion and isoflurane administration were adjusted to achieve suitable anesthetic depth. All calves received 100% oxygen and were mechanically ventilated to maintain end-tidal carbon dioxide concentrations from 35 to 40 mm Hg and underwent laparoscopic bladder surgery through an abdominal approach. Cardiopulmonary variables were measured before induction and at intervals up to 90 minutes after anesthetic induction.
Results—The quality of induction was excellent in all calves. The XGK requirements were 0.57 ± 0.18 mL/kg and 2.70 ± 0.40 mL/kg/h to induce and maintain anesthesia, respectively. Heart rate was significantly lower than baseline throughout the anesthetic period in the XGK group. Systolic arterial blood pressure was significantly higher in the XGK group, compared with the isoflurane group, from 5 to 90 minutes. Cardiac index was lower than baseline in both groups. Differences between groups in cardiac index and arterial blood gas values were not significant.
Conclusions and Clinical Relevance—Administration of XGK resulted in excellent anesthetic induction and maintenance with cardiopulmonary alterations similar to those associated with isoflurane in mechanically ventilated calves.
Evaluation of a bench-top coagulation analyzer for measurement of prothrombin time, activated partial thromboplastin time, and fibrinogen concentrations in healthy dogs
Authors: Mineo Heather K. , Garabed Rebecca B. 
Published: December 2007

Abstract
Objective—To evaluate a bench-top coagulation analyzer for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen concentration in healthy dogs.
Animals—55 healthy adult dogs.
Procedures—PT, APTT, and fibrinogen concentration were determined by use of the coagulation analyzer. Values were compared with results obtained independently by a conventional laboratory.
Results—Correlations (with 95% confidence intervals) between the coagulation analyzer and conventional laboratory values were 0.760 (0.610 to 0.857), 0.700 (0.448 to 0.721), and 0.896 (0.878 to 0.918) for PT, APTT, and fibrinogen concentration, respectively. Using linear regression, comparison of data from the coagulation analyzer and the conventional laboratory provided equations relating the coagulation analyzer values with values from the conventional laboratory and suggested that APTT and fibrinogen values from the coagulation analyzer and conventional laboratory were approximately the same within expected random variation. Prothrombin time values for the coagulation analyzer were significantly offset from the PT values for the conventional laboratory but still were correlated reasonably well with the conventional laboratory values.
Conclusions and Clinical Relevance—By use of the mechanical method of analysis, fibrinogen concentrations obtained with a bench-top coagulation analyzer correlated well with results for a conventional laboratory, indicating that the coagulation analyzer is a reliable instrument for determination of this coagulation variable. Coagulation analyzer results for PT and APTT correlated less strongly with those for the conventional laboratory, but they would still be considered clinically reliable.
Epidemiologic characteristics of catastrophic musculoskeletal injuries in Thoroughbred racehorses
Authors: Cruz Antonio M. , Poljak Zvonimir , Filejski Catherine , Lowerison Mark L. , Goldie Kyle , Martin S. Wayne , Hurtig Mark B. 
Published: December 2007

Abstract
Objective—To determine characteristics, incidence rate, and possible associations with selected demographic characteristics of catastrophic musculoskeletal injuries (CMIs) in Thoroughbred racehorses.
Animals—76 Thoroughbreds with CMIs.
Procedures—Incidence rates of CMIs during racing or training were calculated with number of CMIs as the numerator and overall numbers of races or training events during 2004 and 2005 as the denominators. Exact 95% confidence intervals were calculated. Associations between incidence and dichotomous exposure factors, nominal factors, and ordinal factors were determined. Only univariable associations were examined.
Results—76 horses were euthanized because of CMI and represented 2.36 and 1.69 deaths/1,000 racing starts in 2004 and 2005, respectively. Of these, 57 were euthanized within 60 days before or after a race, which yielded a point incidence of 1.05/1,000 racing starts and 0.39/1,000 training starts.
Conclusions and Clinical Relevance—Incidence rate of CMIs at 2 Ontario racetracks was similar to that at other North American racetracks. A cumulative death rate of 1 to 2 deaths/wkshould be considered typical when designing prevention strategies and offers a baseline value for measuring improvement.
Telomere length in normal and neoplastic canine tissues
Authors: Cadile Casey D. , Kitchell Barbara E. , Newman Rebecca G. , Biller Barbara J. , Hetler Elizabeth R. 
Published: December 2007

Abstract
Objective—To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues.
Sample Population—57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs.
Procedures—Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois.
Results—Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length.
Conclusions and Clinical Relevance—Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human antitelomerase strategies.
Comparison of the effects of caffeine and doxapram on respiratory and cardiovascular function in foals with induced respiratory acidosis
Authors: Giguère Steeve , Sanchez L. Chris , Shih Andre , Szabo Nancy J. , Womble Ariel Y. , Robertson Sheilah A. 
Published: December 2007

Abstract
Objective—To determine and compare the effects of caffeine and doxapram on cardiorespiratory variables in foals during isoflurane-induced respiratory acidosis.
Animals—6 clinically normal foals (1 to 3 days old).
Procedures—At intervals of ≥ 24 hours, foals received each of 3 IV treatments while in a steady state of hypercapnia induced by isoflurane anesthesia (mean ± SD, 1.4 ± 0.3% endtidal isoflurane concentration). After assessment of baseline cardiorespiratory variables, a low dose of the treatment was administered and variables were reassessed; a high dose was then administered, and variables were again assessed. Sequential low- and high-dose treatments included doxapram (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl) solution (equivalent volumes).
Results—Administration of doxapram at both infusion rates resulted in a significant increase in respiratory rate, minute ventilation, arterial blood pH, PaO2, and arterial blood pressure. These variables were also significantly higher during doxapram administration than during caffeine or saline solution administration. There was a significant dose-dependent decrease in PaCO2 and arterial bicarbonate concentration during doxapram treatment. In contrast, PaCO2 increased from baseline values after administration of saline solution or caffeine. The PaCO2 value was significantly lower during doxapram treatment than it was during caffeine or saline solution treatment.
Conclusions and Clinical Relevance—Results indicated that doxapram restored ventilation in a dose-dependent manner in neonatal foals with isoflurane-induced hypercapnia. The effects of caffeine on respiratory function were indistinguishable from those of saline solution.
Fetal protection against continual exposure to bovine viral diarrhea virus following administration of a vaccine containing an inactivated bovine viral diarrhea virus fraction to cattle
Authors: Grooms Daniel L. , Bolin Steven R. , Coe Paul H. , Borges Rafael J. , Coutu Christopher E. 
Published: December 2007

Abstract
Objective—To evaluate the efficacy of a commercially available killed bovine viral diarrhea virus (BVDV) vaccine to protect against fetal infection in pregnant cattle continually exposed to cattle persistently infected with the BVDV.
Animals—60 crossbred beef heifers and 4 cows persistently infected with BVDV.
Procedures—Beef heifers were allocated to 2 groups. One group was vaccinated twice (21-day interval between the initial and booster vaccinations) with a commercially available vaccine against BVDV, and the other group served as nonvaccinated control cattle. Estrus was induced, and the heifers were bred. Pregnancy was confirmed by transrectal palpation. Four cows persistently infected with BVDV were housed with 30 pregnant heifers (15 each from the vaccinated and nonvaccinated groups) from day 52 to 150 of gestation. Fetuses were then harvested by cesarean section and tested for evidence of BVDV infection.
Results—1 control heifer aborted after introduction of the persistently infected cows. Bovine viral diarrhea virus was isolated from 14 of 14 fetuses obtained via cesarean section from control heifers but from only 4 of 15 fetuses obtained via cesarean section from vaccinated heifers; these proportions differed significantly.
Conclusions and Clinical Relevance—A commercially available multivalent vaccine containing an inactivated BVDV fraction significantly reduced the risk of fetal infection with BVDV in heifers continually exposed to cattle persistently infected with BVDV. However, not all vaccinated cattle were protected, which emphasizes the need for biosecurity measures and elimination of cattle persistently infected with BVDV in addition to vaccination within a herd.
Petitions for Extreme Risk Protection Orders and Second Amendment Sanctuary Status in Colorado
Authors: Knoepke Christopher E. , Barnard Leslie M. , Batta Nisha , McCarthy Megan , Thies Kimberly , Olivencia Christian , Robinson Caitlin , Kettering Shalyn , Huss Sheila , Betz Marian E. 
Published: April 2024

ImportanceExtreme risk protection orders (ERPOs) temporarily bar individuals adjudicated as being at risk of violence (including suicide) from buying or possessing firearms. In protest, many US jurisdictions have declared themselves “Second Amendment sanctuaries” (2A sanctuaries). Many 2A sanctuaries continue to use ERPOs in low numbers, suggesting a poorly defined risk threshold at which they are acceptable.ObjectiveTo characterize circumstances under which ERPOs are used in 2A sanctuaries, highlighting their most broadly acceptable applications.Design, Setting, and ParticipantsThis cross-sectional study of civil court documents analyzed petitions for ERPOs filed in Colorado from January 2020 to December 2022. All petitions during the study period were included following de-duplication. These include petitions filed by law enforcement and family members against adults allegedly at risk of firearm violence across the state. Data were analyzed on a rolling basis between January 2020 and June 2023.ExposureERPO petition filed in Colorado.Main Outcomes and MeasuresSeventy-seven data elements defined a priori were abstracted from all petitions and case files, including respondent demographics, petitioner types (family or law enforcement), types of threats (self, other, mass violence, combination), violence risk factors, and case outcomes (granted, denied).ResultsOf a total 338 ERPOs filed in Colorado, 126 (37.3%) occurred in 2A sanctuaries. Sixty-one of these 2A petitions were granted emergency orders, and 40 were full 1-year ERPOs after a hearing. Forty ERPOs (31.7%) were petitioned for by law enforcement. Petitions in non-2A counties were more likely to have been filed by law enforcement (138 of 227 [64.9%] vs 40 of 126 [31.7%]; P &amp;lt; .001) and to have had an emergency order granted (177 of 227 [78.0%] vs 61 of 126 [48.4%]; P &amp;lt; .001) than in 2A sanctuaries. Qualitative analysis of cases in 2A sanctuaries revealed common aggravating risk characteristics, including respondents experiencing hallucinations, histories of police interaction, and substance misuse. ERPOs have been granted in 2A sanctuaries against individuals threatening all forms of violence we abstracted for (themselves, others, and mass violence).Conclusions and RelevanceIn this examination of ERPO petitions across Colorado, more than a third of filings occurred in 2A sanctuaries. Nonetheless, law enforcement represent proportionately fewer petitions in these areas, and petitions are less likely to be granted. Serious mental illness, substance misuse, and prior interactions with law enforcement featured prominently in 2A sanctuary petitions. These case circumstances highlight dangerous situations in which ERPOs are an acceptable risk-prevention tool, even in areas politically predisposed to opposing them.
Unraveling Surface Reconstruction During Oxygen Evolution Reaction on the Defined Spinel Oxide Surface
Authors: Yeom Kyungbeen , Jo Jinwoung , Shin Heejong , Ji Hyunsoo , Moon Sungjin , Park Ji Eun , Lee Seongbeom , Shim Jaehyuk , Mok Dong Hyeon , Bootharaju Megalamane S. , Back Seoin , Hyeon Taeghwan , Sung Yung‐Eun 
Published: April 2024

AbstractThe reconstructed surface structure of Co‐based spinel oxides serves as the active site for oxygen evolution reaction (OER). However, the structural complexity of spinel oxides and surface dynamics during the OER hinder the understanding of the reconstruction mechanism and electronic structure of the active site. In this study, spinel Co3O4@(CoFeV)3O4 nanocube (CoFeV) is reported, a (001) facet‐defined spinel oxide comprising Co, Fe, and V deposited on the Co3O4 nanocube template to exclude facet‐dependent factors. Introducing highly dissoluble V cations accelerates the reconstruction process to enhance the electrocatalytic activity. CoFeV exhibited enhanced electrocatalytic activity (266 mV at 10 mA cm−2 in 1 M KOH) and durability (maintained stable electrocatalytic activity during a 200 h chronopotentiometry (CP) test at 100 mA cm−2) with significantly enlarged electrochemically active surface area (ECSA). The experimental and theoretical results demonstrated that V dissolution during catalysis induced oxygen vacancies, accelerating the surface reconstruction to highly active oxyhydroxide. Consequently, the anion exchange membrane water electrolyzer (AEMWE) of CoFeV as the anode exhibited a remarkable performance of 6.19 A cm−2 at 2.0 Vcell in 1 M KOH and robust durability for 96 h at a constant current density of 500 mA cm−2.