bluuebunny/crossref_metadata_2025_split huggingface dataset:
KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activityin vitroandin vivo
Authors: Hassig Christian A. , Symons Kent T. , Guo Xin , Nguyen Phan-Manh , Annable Tami , Wash Paul L. , Payne Joseph E. , Jenkins David A. , Bonnefous Céline , Trotter Carol , Wang Yan , Anzola John V. , Milkova Elena L. , Hoffman Timothy Z. , Dozier Sara J. , Wiley Brandon M. , Saven Alan , Malecha James W. , Davis Robert L. , Muhammad Jerry , Shiau Andrew K. , Noble Stewart A. , Rao Tadimeti S. , Smith Nicholas D. , Hager Jeffrey H. 
Published: May 2008

AbstractHistone deacetylase (HDAC) inhibitors have garnered significant attention as cancer drugs. These therapeutic agents have recently been clinically validated with the market approval of vorinostat (SAHA, Zolinza) for treatment of cutaneous T-cell lymphoma. Like vorinostat, most of the small-molecule HDAC inhibitors in clinical development are hydroxamic acids, whose inhibitory activity stems from their ability to coordinate the catalytic Zn2+ in the active site of HDACs. We sought to identify novel, nonhydroxamate-based HDAC inhibitors with potentially distinct pharmaceutical properties via an ultra-high throughput small molecule biochemical screen against the HDAC activity in a HeLa cell nuclear extract. An α-mercaptoketone series was identified and chemically optimized. The lead compound, KD5170, exhibits HDAC inhibitory activity with an IC50 of 0.045 μmol/L in the screening biochemical assay and an EC50 of 0.025 μmol/L in HeLa cell–based assays that monitor histone H3 acetylation. KD5170 also exhibits broad spectrum classes I and II HDAC inhibition in assays using purified recombinant human isoforms. KD5170 shows significant antiproliferative activity against a variety of human tumor cell lines, including the NCI-60 panel. Significant tumor growth inhibition was observed after p.o. dosing in human HCT-116 (colorectal cancer), NCI-H460 (non–small cell lung carcinoma), and PC-3 (prostate cancer) s.c. xenografts in nude mice. In addition, a significant increase in antitumor activity and time to end-point occurred when KD5170 was combined with docetaxel in xenografts of the PC-3 prostate cancer cell line. The biological and pharmaceutical profile of KD5170 supports its continued preclinical and clinical development as a broad spectrum anticancer agent. [Mol Cancer Ther 2008;7(5):1054–65]
SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells
Authors: Vultur Adina , Buettner Ralf , Kowolik Claudia , Liang Wei , Smith David , Boschelli Frank , Jove Richard 
Published: May 2008

Abstract
Src family kinase activity is elevated in many human tumors, including breast cancer, and is often associated with aggressive disease. We examined the effects of SKI-606 (bosutinib), a selective Src family kinase inhibitor, on human cancer cells derived from breast cancer patients to assess its potential for breast cancer treatment. Our results show that SKI-606 caused a decrease in cell motility and invasion of breast cancer cell lines with an IC50 of ∼250 nmol/L, which was also the IC50 for inhibition of cellular Src kinase activity in intact tumor cells. These changes were accompanied by an increase in cell-to-cell adhesion and membrane localization of β-catenin. By contrast, cell proliferation and survival were unaffected by SKI-606 at concentrations sufficient to block cell migration and invasion. Analysis of downstream effectors of Src revealed that SKI-606 inhibits the phosphorylation of focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2), and Crk-associated substrate (p130Cas), with an IC50 similar to inhibition of cellular Src kinase. Our findings indicate that SKI-606 inhibits signaling pathways involved in controlling tumor cell motility and invasion, suggesting that SKI-606 is a promising therapeutic for breast cancer. [Mol Cancer Ther 2008;7(5):1185–94]
Cash and Kin Go to Court: Legal Families and Chosen Families in Nineteenth-Century Egypt
Authors: Ghazaleh Pascale 
Published: May 2008

AbstractCourt records have offered historians an unparalleled source of information about the Ottoman period, particularly in the Empire's Arab provinces, where abundant documentation tells us about society's material conditions. As far as family history is concerned, Ottoman courts have yielded much important information regarding women's rights and status, as revealed in marriage contracts recorded before the Ottoman qadi. In the field of economic and social history, estate inventories have offered a glimpse of how people lived, what they might have consumed, and how wealthy they were. To date, however, less work has been done on how the family was structured by material relations, as indicated by financial transfers carried out upon a family member's death. In my paper, I will follow some of these transfers, in the form of pre-mortem gifts as well as post-mortem bequests, in an attempt to understand how individuals expressed their sense of obligation toward different elements in their social universe. I will seek to demonstrate that cash flows indicate individual preferences regarding the beneficiaries of wealth. I will also examine the relative importance of different associations, both kin and non-kin, in an individual's social network.
Genesis 1-3 as Source for the Anthropology of Origen
Authors: Lund Jacobsen Anders 
Published: May 2008

AbstractAccording to Origen Genesis 1-3 is an anthropological key-text. The account of man's creation in Gen. 1,26f deals with the creation of the inner non-material man in the image of God, whereas Gen. 2,7 deals with the creation of the human body, the outer man, which is not created in the image of God. Some later critics claim that according to Origen Gen. 2,7 is about the creation of a non-material luminous body. In Origen's opinion only the inner man can reach perfection. The outer man can never be perfect, but will be destroyed. To deepen our understanding of, how Origen understands the mortality of the human body, some short sayings about the meaning of Gen. 3,21 are interpreted. In the few places where Origen refers explicitly to Gen. 3,21 there is no clear picture of how he interprets this verse. The most precise observation we can make is that in his view the skin coats denote the mortal corporality that surrounds the inner man.
Le Paraclet dans la notice antimontaniste du PseudoHippolyte, Refutatio omnium haeresium VIII, 19 Les commentaires prophétiques de Priscilla et Maximilla
Authors: Pastorelli David 
Published: May 2008

AbstractThe anti-Montanist notice of Pseudo-Hippolytus, Ref. VIII, 19 is often quoted in research in order to show that the Phrygian prophets wrote numerous books to complete the New Testament. It is, however, marked by an obvious editorial activity: the motive of countless books belongs to the author's heresiological arsenal and should not be counted as a testimony for the history of the New Testament canon. The author is more concerned about the issue of women's ministry : the conflict is on the one hand about the status of Priscilla and Maximilla as prophetic teachers, based on the prophetic office of the Paraclete, and on the other hand about their claims to write « prophetic » commentaries. The underlying principle is the Pauline prohibition that women teach, a fortiori that they write books.
The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention
Authors: Gerber David E. , Segal Jodi B. , Levy M. Yair , Kane Joyce , Jones Richard J. , Streiff Michael B. 
Published: May 2008

AbstractVenous thromboembolism (VTE) is increasingly diagnosed among individuals with hematologic malignancies. However, the risk of VTE among patients undergoing hematopoietic stem cell transplantation (HSCT) is unclear. We examined the incidence and risk factors for VTE and bleeding among 1514 patients undergoing in-patient HSCT. No protocolized VTE prophylaxis was used. By HSCT day 180, 75 symptomatic VTE occurred in 70 patients (4.6%; 95% confidence interval [CI], 3.6%-5.8%). Fifty-five (3.6%) were catheter-associated, 11 (0.7%) were non–catheter-associated deep venous thromboses, and 9 (0.6%) were pulmonary emboli. Thirty-four percent of VTE occurred at a platelet count less than 50 ×109/L; 13% occurred at a platelet count less than 20 ×109/L. In multivariate analysis, VTE was associated with prior VTE (odds ratio [OR], 2.9; 95% CI, 1.3-6.6) and with graft-versus-host disease (GVHD; OR, 2.4; 95% CI, 1.4-4.0). Clinically significant bleeding occurred in 230 patients (15.2%; 95% CI, 13.4%-17.1%); 55 patients (3.6%; 95% CI, 2.7%-4.7%) had fatal bleeding. Bleeding was associated with anticoagulation (OR, 3.1; 95% CI, 1.8-5.5), GVHD (OR, 2.4; 95% CI, 1.8-3.3), and veno-occlusive disease (OR, 2.2; 95% CI, 1.4-3.6). In HSCT patients, VTE is primarily catheter-related and 3-fold less common than clinically significant bleeding. These findings warrant consideration when selecting VTE prophylaxis in HSCT patients.
Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets
Authors: Dona Maria , Fredman Gabrielle , Schwab Jan M. , Chiang Nan , Arita Makoto , Goodarzi Ahmad , Cheng Guiying , von Andrian Ulrich H. , Serhan Charles N. 
Published: May 2008

AbstractResolvin E1 (RvE1) is an omega-3 eicosapentaenoic acid (EPA)–derived lipid mediator generated during resolution of inflammation and in human vasculature via leukocyte-endothelial cell interactions. RvE1 possesses anti-inflammatory and proresolving actions. Here, we report that RvE1 in human whole blood rapidly regulates leukocyte expression of adhesion molecules. RvE1 in the 10- to 100-nM range stimulated L-selectin shedding, while reducing CD18 expression in both neutrophils and monocytes. When added to whole blood, RvE1 did not stimulate reactive oxygen species by either neutrophils or monocytes, nor did it directly stimulate cytokine/chemokine production in heparinized blood. Intravital microscopy (IVM) demonstrated that RvE1 rapidly reduced leukocyte rolling (∼ 40%) in venules of mice. In human platelet-rich plasma (PRP), RvE1 selectively blocked both ADP-stimulated and thromboxane receptor agonist U46619-stimulated platelet aggregation in a concentration-dependent manner. In contrast, Δ6,14-trans-RvE1 isomer was inactive. RvE1 did not block collagen-stimulated aggregation, and regulation of ADP-induced platelet aggregation was not further enhanced with aspirin treatment. These results indicate RvE1 is a potent modulator of leukocytes as well as selective platelet responses in blood and PRP, respectively. Moreover, the results demonstrate novel agonist-specific antiplatelet actions of RvE1 that are potent and may underlie some of the beneficial actions of EPA in humans.
Validation of a single-channel airflow monitor for screening of sleep-disordered breathing
Authors: Nakano H. , Tanigawa T. , Ohnishi Y. , Uemori H. , Senzaki K. , Furukawa T. , Nishima S. 
Published: May 2008

A simple screening method for sleep-disordered breathing (SDB) is desirable for primary care practices. In the present study, a simple monitor, which utilises a new type of flow sensor and a novel algorithm, was prospectively validated.Home recording for 2 nights with the monitor only, followed by in-laboratory recording with the monitor together with polysomnography, were carried out in consecutive patients (n = 100) suspected of SDB. A subjective sleep log was also recorded. The signal was analysed using power spectral analysis, which yielded the flow respiratory disturbance index (flow-RDI).There was no recording failure at home. The reproducibility of the flow-RDI between the 2 nights at home was high (intraclass correlation coefficient = 0.92). The sensitivity and specificity of the in-laboratory flow-RDI to diagnose SDB were 0.96 and 0.82, 0.91 and 0.82, and 0.89 and 0.96, for apnoea/hypopnoea index (AHI) ≥5, ≥15 and ≥30 events·h−1, respectively. The diagnostic ability in low-severity subgroups (female, normal weight, AHI <15 events·h−1) was almost comparable to that in the entire group. Excluding subjective waking time on the sleep log from the recording time had no significant effect on the flow-RDI.The single-channel monitor is considered feasible for ambulatory sleep disordered breathing monitoring because of its easy applicability, high reproducibility and relatively high agreement with polysomnography results.
Analysis of Aspergillus nidulans metabolism at the genome-scale
Authors: David Helga , Özçelik İlknur Ş , Hofmann Gerald , Nielsen Jens 
Published: May 2008

Abstract

Background

Aspergillus nidulans is a member of a diverse group of filamentous fungi, sharing many of the properties of its close relatives with significance in the fields of medicine, agriculture and industry. Furthermore, A. nidulans has been a classical model organism for studies of development biology and gene regulation, and thus it has become one of the best-characterized filamentous fungi. It was the first Aspergillus species to have its genome sequenced, and automated gene prediction tools predicted 9,451 open reading frames (ORFs) in the genome, of which less than 10% were assigned a function.

Results
In this work, we have manually assigned functions to 472 orphan genes in the metabolism of A. nidulans, by using a pathway-driven approach and by employing comparative genomics tools based on sequence similarity. The central metabolism of A. nidulans, as well as biosynthetic pathways of relevant secondary metabolites, was reconstructed based on detailed metabolic reconstructions available for A. niger and Saccharomyces cerevisiae, and information on the genetics, biochemistry and physiology of A. nidulans. Thereby, it was possible to identify metabolic functions without a gene associated, and to look for candidate ORFs in the genome of A. nidulans by comparing its sequence to sequences of well-characterized genes in other species encoding the function of interest. A classification system, based on defined criteria, was developed for evaluating and selecting the ORFs among the candidates, in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene expression data concerning a study on glucose repression, thereby providing a means of upgrading the information content of experimental data and getting further insight into this phenomenon in A. nidulans.

Conclusion
We demonstrate how pathway modeling of A. nidulans can be used as an approach to improve the functional annotation of the genome of this organism. Furthermore we show how the metabolic model establishes functional links between genes, enabling the upgrade of the information content of transcriptome data.
Cultures in Conflict: An Argument Against “Common Ground” Between Practicing Professional Historians and Academics
Authors: HOLL JACK M. 
Published: May 2008

Abstract
There is a fundamental distinction between practicing professional historians and academics, and any celebration of a “common ground” tradition masks the fundamental cultural differences between historians who practice and historians who teach. Over the past three decades, since the founding of the Society for History in the Federal Government and the National Council on Public History, practicing professional historians have struggled with definitions of public history. “Struggling with our own identify,” the author states, “many federal historians did not want to be labeled public historians, the professor's euphemism for non-academic historians.” Rather, federal historians belonged to a “cadre of professionals who practiced their specialties in the public sector.” With extensive knowledge of the federal history sector (with particular attention given to the historical office of the Department of Energy) as well as academic history departments and policies, the author argues that “professional historians [should] be defined by what they do, rather than by where they work.” The historical profession must acknowledge that federal and other professional historians “occupy their own solid ground, perhaps not adequately mapped,” and represent more than a “middle ground” between the public and the academy.
Building a Model Public History Program: The Office of the Historian at the U.S. Department of State
Authors: AHLBERG KRISTIN L. 
Published: May 2008

Abstract
The Office of the Historian at the U.S. Department of State, responsible for the production and publication of the Foreign Relations of the United States series, has survived hard times with respect to human and financial resources and public criticism, in the last decade of the twentieth century, to emerge as a model for the conduct of public history at the onset of the twenty-first century. The Office meets the mission of the State Department by providing policy-supportive historical studies for the Secretary of State, other State Department principals, and the White House and by engaging in an ever-expanding series of historical outreach programs aimed at new and old audiences. Serving its institutional client in this way has allowed the Office to increase its connections and find common ground not only with diplomatic historians but also with public historians and others in the larger historical profession.
Evaluation of a point-of-care hematology analyzer for use in dogs and cats receiving chemotherapeutic treatment
Authors: Lara-Garcia Ana , Hosoya Kenji , Iazbik Cristina , Westendorf Nicole , Gallant Stacey , Couto Guillermo 
Published: May 2008

Abstract
Objective—To compare WBC, neutrophil, and platelet counts and Hct values obtained with a point-of-care hematology analyzer with values obtained by a reference method for dogs and cats receiving chemotherapy.
Design—Cross-sectional study.
Animals—105 dogs and 25 cats undergoing chemotherapy.
Procedures—Blood samples were analyzed with a point-of-care hematology analyzer and with an impedance- and laser-based analyzer with manual differential WBC counts. Results for WBC, neutrophil, and platelet counts and Hct were compared. Sensitivity and specificity of the point-of-care analyzer to detect leukopenia, neutropenia, and anemia were calculated.
Results—554 canine and 96 feline blood samples were evaluated. Correlation coefficients for dogs and cats, respectively, were 0.92 and 0.95 for total WBC count, 0.91 and 0.88 for neutrophil count, 0.95 and 0.92 for Hct, and 0.93 and 0.71 for platelet count. Sensitivity and specificity, respectively, of the point-of-care analyzer to detect leukopenia were 100% and 75% for dogs and 100% and 68% for cats; to detect neutropenia were 80% and 97% for dogs and 100% and 80% for cats; to detect anemia were 100% and 80% for dogs and 100% and 66% for cats; and to detect thrombocytopenia were 86% and 95% for dogs and 50% and 87% for cats.
Conclusions and Clinical Relevance—The point-of-care analyzer was reliable for monitoring CBCs of dogs and cats receiving chemotherapy. It had good to excellent correlation for WBC and neutrophil counts and Hct and accurately detected leukopenia, neutropenia, and anemia. Sensitivity of the analyzer for detecting thrombocytopenia was lower but acceptable.
Clinical utility of serum N-terminal pro-B-type natriuretic peptide concentration for identifying cardiac disease in dogs and assessing disease severity
Authors: Oyama Mark A. , Fox Philip R. , Rush John E. , Rozanski Elizabeth A. , Lesser Mike 
Published: May 2008

Abstract
Objective—To determine whether serum N-terminal pro-B-type natriuretic (NT-proBNP) concentration could be used to identify cardiac disease in dogs and to assess disease severity in affected dogs.
Design—Cross-sectional study.
Animals—119 dogs with mitral valve disease, 18 dogs with dilated cardiomyopathy, and 40 healthy control dogs.
Procedures—Serum NT-proBNP concentration was measured with an ELISA validated for use in dogs. Results of physical examination, thoracic radiography, echocardiography, and serum biochemical analyses were recorded for dogs with cardiac disease.
Results—Serum NT-proBNP concentration was significantly higher in dogs with cardiac disease than in control dogs, and a serum NT-proBNP concentration > 445 pmol/L could be used to discriminate dogs with cardiac disease from control dogs with a sensitivity of 83.2% and specificity of 90.0%. In dogs with cardiac disease, serum NT-proBNP concentration was correlated with heart rate, respiratory rate, echocardiographic heart size, and renal function. For dogs with cardiac disease, serum NT-proBNP concentration could be used to discriminate dogs with and without radiographic evidence of cardiomegaly and dogs with and without congestive heart failure.
Conclusions and Clinical Relevance—Results suggested that serum NT-proBNP concentration may be a useful adjunct clinical test for diagnosing cardiac disease in dogs and assessing the severity of disease in dogs with cardiac disease.
Intralesional injection of platelet-rich plasma followed by controlled exercise for treatment of midbody suspensory ligament desmitis in Standardbred racehorses
Authors: Waselau Martin , Sutter W. Wesley , Genovese Ronald L. , Bertone Alicia L. 
Published: May 2008

Abstract
Objective—To determine outcome of Standardbred racehorses with moderate to severe midbody suspensory ligament desmitis (MSD) treated by means of ultrasound-guided intralesional injection of a single dose of platelet-rich plasma (PRP) followed by a program of gradually increased exercise.
Design—Nonrandomized clinical trial.
Animals—9 Standardbred racehorses.
Procedures—Following injection of PRP, horses were allowed a controlled, gradual return to exercise. Race records for the year prior to injury and for 3 consecutive years after horses returned to racing were reviewed. For comparison purposes, race records of 9 Standardbred racehorses with no history of MSD racing at the same time were also reviewed.
Results—All 9 horses with MSD returned to racing after treatment; median time to return to racing was 32 weeks. All 9 horses raced at least once during the first and second years after returning to racing, but only 5 raced during the third year. When number of starts, total earnings, and earnings per start were compared between case and comparison horses, the only significant differences were number of starts during the third year after case horses returned to racing and earnings per start during the first year after case horses returned to racing, with values being significantly lower for case horses than for comparison horses.
Conclusions and Clinical Relevance—Results suggested that horses with moderate to severe MSD treated by means of intralesional injection of a single dose of PRP followed by a program of gradually increased exercise had an excellent prognosis for returning to racing.