bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Maturation Inhibitor Bevirimat Stabilizes the Immature Gag Lattice
Authors: Keller Paul W. , Adamson Catherine S. , Heymann J. Bernard , Freed Eric O. , Steven Alasdair C. 
Published: November 2010

ABSTRACT
Maturation of nascent virions, a key step in retroviral replication, involves cleavage of the Gag polyprotein by the viral protease into its matrix (MA), capsid (CA), and nucleocapsid (NC) components and their subsequent reorganization. Bevirimat (BVM) defines a new class of antiviral drugs termed maturation inhibitors. BVM acts by blocking the final cleavage event in Gag processing, the separation of CA from its C-terminal spacer peptide 1 (SP1). Prior evidence suggests that BVM binds to Gag assembled in immature virions, preventing the protease from accessing the CA-SP1 cleavage site. To investigate this hypothesis, we used cryo-electron tomography to examine the structures of (noninfectious) HIV-1 viral particles isolated from BVM-treated cells. We find that these particles contain an incomplete shell of density underlying the viral envelope, with a hexagonal honeycomb structure similar to the Gag lattice of immature HIV but lacking the innermost, NC-related, layer. We conclude that the shell represents a remnant of the immature Gag lattice that has been processed, except at the CA-SP1 sites, but has remained largely intact. We also compared BVM-treated particles with virions formed by the mutant CA5, in which cleavage between CA and SP1 is also blocked. Here, we find a thinner CA-related shell with no visible evidence of honeycomb organization, indicative of an altered conformation and further suggesting that binding of BVM stabilizes the immature lattice. In both cases, the observed failure to assemble mature capsids correlates with the loss of infectivity.
Krasnosel'skii-Type Fixed-Set Results
Authors: Al-Thagafi MA , Shahzad Naseer 
Published: November 2010

AbstractSome new Krasnosel'skii-type fixed-set theorems are proved for the sum "Equation missing", where "Equation missing" is a multimap and "Equation missing" is a self-map. The common domain of "Equation missing" and "Equation missing" is not convex. A positive answer to Ok's question (2009) is provided. Applications to the theory of self-similarity are also given.
Longitudinal Investigation of Permeability and Distribution of Macromolecules in Mouse Malignant Transformation Using PET
Authors: Rygh Cecilie B. , Qin Shengping , Seo Jai W. , Mahakian Lisa M. , Zhang Hua , Adamson Roger , Chen Jane Q. , Borowsky Alexander D. , Cardiff Robert D. , Reed Rolf K. , Curry Fitz-Roy E. , Ferrara Katherine W. 
Published: November 2010

Abstract
Purpose: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease.
Experimental Design: Albumin and liposomes were labeled with 64Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability.
Results: From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10−8 and 1.3 × 10−8 cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin.
Conclusions: PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability. Clin Cancer Res; 17(3); 550–9. ©2010 AACR.
Dasatinib Plus Nutlin-3 Shows Synergistic Antileukemic Activity in Both p53wild-type and p53mutated B Chronic Lymphocytic Leukemias by Inhibiting the Akt Pathway
Authors: Zauli Giorgio , Voltan Rebecca , Bosco Raffaella , Melloni Elisabetta , Marmiroli Sandra , Rigolin Gian Matteo , Cuneo Antonio , Secchiero Paola 
Published: November 2010

Abstract
Purpose: To analyze the effect of the combination of Dasatinib, a multikinase inhibitor, plus Nutlin-3, a nongenotoxic activator of the p53 pathway, in primary B chronic lymphocytic leukemia (B-CLL) patient samples and B leukemic cell line models.
Experimental Design: The induction of cytotoxicity was evaluated in both primary B-CLL cell samples (n = 20) and in p53wild-type (EHEB, JVM-2) and p53deleted/mutated (MEC-2, BJAB) B leukemic cell lines. The role of Akt in modulating leukemic cell survival/apoptosis in response to Dasatinib or Dasatinib + Nutlin-3 was documented by functional experiments carried out using specific pharmacological inhibitors and by overexpression of membrane-targeted constitutively active form of Akt.
Results: The combination of Dasatinib + Nutlin-3 exhibited a synergistic cytotoxicity in the majority (19 out of 20) of B-CLL samples, including patients carrying 17p- (n = 4), and in both p53wild-type and p53deleted/mutated B leukemic cell lines. At the molecular level, Dasatinib significantly counteracted the Nutlin-3-mediated induction of the p53 transcriptional targets MDM2 and p21 observed in p53wild-type leukemic cells. Conversely, Nutlin-3 did not interfere with the ability of Dasatinib to decrease the phosphorylation levels of ERK1/2, p38/MAPK, and Akt in both p53wild-type and p53deleted/mutated B leukemic cell lines. A critical role of Akt downregulation in mediating the antileukemic activity of Dasatinib and Dasatinib + Nutlin-3 was demonstrated in experiments carried out by specifically modulating the Akt pathway.
Conclusions: These findings suggest that Dasatinib + Nutlin-3 might represent an innovative therapeutic combination for both p53wild-type and p53deleted/mutated B-CLL. Clin Cancer Res; 17(4); 1–9. ©2010 AACR.
Estrogen Receptor Polymorphisms and the Vascular Effects of Hormone Therapy
Authors: Rossouw Jacques , Bray Paul , Liu Jingmin , Kooperberg Charles , Hsia Judith , Lewis Cora , Cushman Mary , Bonds Denise , Hendrix Susan , Papanicolaou George , Howard Timothy , Herrington David 
Published: November 2010

Objective—
To test whether estrogen receptor polymorphisms modify the effects of postmenopausal hormone therapy on biomarkers and on risk of coronary heart disease events, stroke, or venous thromboembolism.

Methods and Results—

The design was a nested case-control study in the Women's Health Initiative trials of postmenopausal hormone therapy. The study included all cases in the first 4 years: 359 cases of coronary heart disease, 248 of stroke, and 217 of venous thromboembolism. Six
estrogen receptor-α
polymorphisms and 1
estrogen receptor-β
polymorphism were genotyped; 8 biomarkers known to be affected by hormone therapy were measured at baseline and 1 year after randomization. The polymorphisms were not associated with risk of vascular events and did not modify the increased risks of coronary heart disease, stroke, or venous thromboembolism due to hormone therapy. However, a reduced response of plasmin-antiplasmin to hormone therapy was noted for
estrogen receptor-1
IVS1 (intron number 1)-354 (interaction
P
<0.0001, corrected for multiple comparisons
P
=0.014) and
estrogen receptor-1
IVS1-1415 (interaction
P
<0.0001, corrected
P
=0.014).

Conclusion—
Estrogen receptor polymorphisms reduce the effect of postmenopausal hormone therapy on plasmin-antiplasmin, a marker of coagulation and fibrinolysis. However, screening for estrogen receptor polymorphisms to identify women at less risk of adverse cardiovascular outcomes is not likely to be useful in making decisions about hormone therapy treatment.
Predictors of Migraine Subtypes in Young Adults With Ischemic Stroke
Authors: Pezzini Alessandro , Grassi Mario , Lodigiani Corrado , Patella Rosalba , Gandolfo Carlo , Casoni Federica , Musolino Rossella , Calabrò Rocco Salvatore , Bovi Paolo , Adami Alessandro , DeLodovici Maria Luisa , Del Zotto Elisabetta , Rota Lidia Luciana , Rasura Maurizia , Del Sette Massimo , Giossi Alessia , Volonghi Irene , Zini Andrea , Cerrato Paolo , Costa Paolo , Magoni Mauro , Iacoviello Licia , Padovani Alessandro ,   on behalf of the Italian Project on Stroke in Young Adults Investigators
Published: November 2010

Background and Purpose—
The mechanisms underlying the relationship between migraine and ischemic stroke remain uncertain. The aim of the present study was to investigate the predictive value of major cardiovascular risk factors, cardiac interatrial abnormalities, and additional biological markers on migraine subtypes in young adults with ischemic stroke.

Methods—
Ischemic stroke patients aged 45 years or younger were consecutively enrolled as part of the Italian Project on Stroke in Young Adults. A comprehensive evaluation was performed including assessment of self-reported migraine and cardiovascular risk factors, interatrial right-to-left shunt, and genotyping to detect factor V Leiden and the G20210A mutation in the prothrombin gene.

Results—
Nine hundred eighty-one patients (mean age, 36.0±7.6 years; 50.7% women) were included. The risk of migraine with aura increased with decreasing number of cardiovascular risk factors (OR, 0.50; 95% CI, 0.24–0.99 for 2 factors or more), increasing number of thrombophilic variants (OR, 2.21; 95% CI, 1.05–4.68 for carriers of at least 1 of the 2), and the presence of right-to-left shunt (OR, 2.41; 95% CI, 1.37–3.45), as compared to patients without migraine. None of these factors had influence on the risk of migraine without aura.

Conclusions—
In young adults with ischemic stroke, low cardiovascular risk profile, right-to-left shunt, and an underlying procoagulant state are predictors of migraine with aura. The biological effects of these factors should be considered in future studies aimed at investigating the mechanisms linking migraine to brain ischemia.
Logic of Science vs. Theory of Creation: The “Authority of Annihilation” in Hermann Cohen’s Logic of Origin
Authors: Wiedebach Hartwig 
Published: November 2010

AbstractThe difference between Hermann Cohen’s systematic philosophy and his philosophy of religion can be determined via the logical “Judgment of Contradiction,” viewed as an “Authority of Annihilation.” In Cohen’s Logic of Pure Knowledge the “Judgment of Contradiction” acts as a “means of protection” against “falsifications” that may have arisen on the pathway through the previous judgments of “origin” and “identity.” Cohen thematizes these operations in his Religion of Reason Out of the Sources of Judaism, too. However, there they do not form the grounding for natural science but rather for the knowledge of nature as creation in a strict correlation to God’s uniqueness. Any admixture between God and nature is the falseness that must be excluded via the “Authority of Annihilation.” The Being of God places the world over against the possibility of its own radical Non-Being. Yet at the same time, a second mode of Negation, a relative Nothing providing continuity for the world’s being-there (Dasein), grounded in the “Logic of Origin,” retains its validity. In Cohen’s view a Creation “in the beginning” stands side by side with a continuous “renewal of the world” (hiddush ha-‘olam).
Emmanuel Levinas’s Geopolitics: Overlooked Conversations between Rabbinical and Third World Decolonialisms
Authors: Slabodsky Santiago 
Published: November 2010

AbstractIn this article, I re-evaluate critiques of Levinas’s Eurocentrism by exploring his openness to decolonial theory. First, I survey Levinas’s conceptual confrontation with imperialism, showing that his early Eurocentric work (1930s‐1960s) is revised in his later writing (1970s‐1980s). Second, I explore the contextual reasons that led him to take that path, such as his previously overlooked conversations with the liberationist South American intellectual Enrique Dussel. Finally, I present the case for a revisitation of the current theoretical frameworks of Jewish thought. I explain how Levinas’s encounter with Third World discourses helps to add a needed decolonial layer to contemporary Jewish intercultural conversations.
Rape: A Problem of Crime Classification in Islamic Law
Authors: Noor Azman Mohd 
Published: November 2010

AbstractIn Islam, rape is considered a serious sexual crime. Since it consists of forced sexual intercourse, most of the classical jurists called it zinā bī l-ikrāh, that is, forced unlawful sexual intercourse. The question arises whether rape is part of zinā or an isolated crime. This article focuses on the notion of rape, including a definition of this crime, its punishments, and a comparison between rape and zinā in Islamic jurisprudence.
Can Electronic Agents Be Granted Legal Personality under Islamic Law? A Conceptual Rethink Is Imperative
Authors: Almajid Walid Mohammed 
Published: November 2010

AbstractMost legislation, whether international or national, deals with electronic agents in a way that does not reflect the certainty of their features. In the past, only a human being could perform the functions that electronic agents do at present. Such electronic agents that are considered ‘Intelligent’ ramble quickly into various places, search for information, and carry out various stages of a transaction from product and merchant brokering through to negotiation, sales, distribution and payment. Nevertheless, legislations have classified them as communication tools. Perhaps such terminology has been chosen because of the lack of difficulty in its implementation or lack of legislation having the legal tools to recognize clearly the acts of electronic agents. In this paper, the concept ‘electronic agent’ is scrutinized and the feasibility of granting them ‘legal personality’ investigated, particularly under Islamic law. In particular, the question is asked: does the concept ‘legal personality’ really exist under Islamic law? If so, then how is it defined? In addition, in light of the definition(s) presented, how can ‘legal personality’ be attributed to electronic agents?
Sharīah and Conventional Law Objections to Derivatives: A Comparison
Authors: Kunhibava Sherin , Shanmugam Balachandran 
Published: November 2010

AbstractIn Islamic finance, many scholars advise against the use of derivatives, which is still in its infancy. Conventional law even voiced its objections to derivatives as early as the 17th century. This article surveys and compares the relationship between present-day legal objections to derivatives in Islamic finance and those objections held in the past by conventional finance. It was found that objections to derivatives, held by both separate fields of finance, show similarities as well as differences. For example, both Islamic and conventional finance object to the gambling nature inherent in derivative trading; in contrast, under Sharīah law, the scope of Islamic finance’s objections is broader, including other elements such as uncertainty and ignorance. Furthermore, Sharīah scholars also object to option trading that requires payment of a fee and to futures trading that involves payment of a debt with a debt.
An Interfaith Encounter at Jacob’s Well A Missiological Interpretation of John 4:4‐42
Authors: Phan Peter C. 
Published: November 2010

AbstractAfter review various approaches and possible interpretations of John 4:4‐42 (i.e., christological, pneumatological, sacramental, liturgical, and feminist), the essay presents a missiological reading of John 4:4‐42. It shows how the text answers questions about the origin, purpose, contents, and fruits of the church’s mission. Finally, it argues that Jesus’ and the Samaritan woman’s mutual interactions represent a possible paradigm for interreligious dialogue which is an essential part of Christian mission.
An investigation of the relationship between subjective sleep quality, loneliness and mood in an Australian sample: Can daily routine explain the links?
Authors: Smith Simon Squire , Kozak Nahum , Sullivan Karen Anne 
Published: November 2010

Background: Loneliness and low mood are associated with significant negative health outcomes including poor sleep, but the strength of the evidence underlying these associations varies. There is strong evidence that poor sleep quality and low mood are linked, but only emerging evidence that loneliness and poor sleep are associated. Aims: To independently replicate the finding that loneliness and poor subjective sleep quality are associated and to extend past research by investigating lifestyle regularity as a possible mediator of relationships, since lifestyle regularity has been linked to loneliness and poor sleep. Methods: Using a cross-sectional design, 97 adults completed standardized measures of loneliness, lifestyle regularity, subjective sleep quality and mood. Results: Loneliness was a significant predictor of sleep quality. Lifestyle regularity was not a predictor of, nor associated with, mood, sleep quality or loneliness. Conclusions: This study provides an important independent replication of the association between poor sleep and loneliness. However, the mechanism underlying this link remains unclear. A theoretically plausible mechanism for this link, lifestyle regularity, does not explain the relationship between loneliness and poor sleep. The nexus between loneliness and poor sleep is unlikely to be broken by altering the social rhythm of patients who present with poor sleep and loneliness.
Using a Cell Phone-Based Glucose Monitoring System for Adolescent Diabetes Management
Authors: Carroll Aaron E. , DiMeglio Linda A. , Stein Stephanie , Marrero David G. 
Published: November 2010

Introduction Mobile technology may be useful in addressing several issues in adolescent diabetes management. Purpose To assess the feasibility and acceptability of a cell phone glucose monitoring system for adolescents with type 1 diabetes and their parents. Methods The authors recruited patients with type 1 diabetes who had been diagnosed for at least 1 year. Each adolescent used the system for 6 months, filling out surveys every 3 months to measure their usability and satisfaction with the cell phone glucose monitoring system, as well as how use of the system might affect quality of family functioning and diabetes management. Results Adolescents reported positive feelings about the technology and the service, even though a concerning number of them had significant technical issues that affected continued use of the device. Nearly all thought that the clinic involvement in monitoring testing behavior was quite acceptable. The use of the Glucophone™ did not, however, significantly change the quality of life of the adolescents, their level of conflict with their parents, their reported self-management of diabetes, or their average glycemic control within the short time frame of the study. Conclusions As a feasibility study of the technology, this work was successful in demonstrating that cell phone glucose monitoring technology can be used in an adolescent population to track and assist in self-monitoring behavior. The authors speculate that explicitly attempting to change behavior, perhaps with the use of behavioral contracts, would enhance the technology’s ability to improve outcomes.
Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial
Authors: Ensor Hannah M. , Schwab Claire , Russell Lisa J. , Richards Sue M. , Morrison Heather , Masic Dino , Jones Lisa , Kinsey Sally E. , Vora Ajay J. , Mitchell Christopher D. , Harrison Christine J. , Moorman Anthony V. 
Published: November 2010

Abstract
Deregulated expression of CRLF2 (CRLF2-d) arises via its juxtaposition to the IGH@ enhancer or P2RY8 promoter. Among 865 BCP-ALL children treated on MRC ALL97, 52 (6%) had CRLF2-d, but it was more prevalent among Down syndrome patients (54%). P2RY8-CRLF2 (n = 43) was more frequent than IGH@-CRLF2 (n = 9). CRLF2-d was not associated with age, sex, or white cell count, but IGH@-CRLF2 patients were older than P2RY8-CRLF2 patients (median 8 vs 4 years, P = .0017). Patients with CRLF2-d were more likely to present with enlarged livers and spleens (38% vs 18%, P < .001). CRLF2-d was not seen in conjunction with established chromosomal translocations but 6 (12%) cases had high hyperdiploidy, and 5 (10%) had iAMP21. Univariate analysis suggested that CRLF2-d was associated with an inferior outcome: (event-free survival [EFS] hazard ratio 2.27 [95% confidence interval 1.48-3.47], P < .001; OS 3.69 [2.34-5.84], P < .001). However, multivariate analysis indicated that its effect was mediated by other risk factors such as cytogenetics and DS status (EFS 1.45 [0.88-2.39], P = .140; OS 1.90 [1.08-3.36], P = .027). Although the outcome of IGH@-CRLF2 patients appeared inferior compared with P2RY8-CRLF2 patients, the result was not significant (EFS 2.69 [1.15-6.31], P = .023; OS 2.86 [1.15-6.79], P = .021). Therefore, we concluded that patients with CRLF2-d should be classified into the intermediate cytogenetic risk group.
Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity
Authors: Offman Marc N. , Krol Marcin , Patel Naina , Krishnan Shekhar , Liu JiZhong , Saha Vaskar , Bates Paul A. 
Published: November 2010

AbstractUsing proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginaseto resist proteolytic cleavage and at the same time improve activity. We employed a novel combination of mutant sampling using a genetic algorithm in tandem with flexibility studies using molecular dynamics to investigate the impact of lid-loop and mutations on drug activity. Applying these methods, we successfully predicted the more active L-asparaginase mutants N24T and N24A. For the latter, a unique hydrogen bond network contributes to higher activity. Furthermore, interface mutations controlling secondary glutaminase activity demonstrated the importance of this enzymatic activity for drug cytotoxicity. All selected mutants were expressed, purified, and tested for activity and for their ability to form the active tetrameric form. By introducing the N24A and N24A R195S mutations to the drug L-asparaginase, we are a step closer to individualized drug design.