bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addisonian Afterlives: Joseph Addison in Eighteenth‐Century Culture
Authors: KLEIN LAWRENCE E. 
Published: September 2011

AbstractEighteenth‐century commentators often used the Bible and sacred inspiration as a tool for measuring the significance of Joseph Addison and his writings. The quasi‐scriptural character of Addison's writings was more than a matter of their popularity; it was an effect of Addison's role in the culture. Aside from being a widely read author and respected normative guide, Addison was taken as a model of social being. The esteem for his writings shaded into an admiration of his personality. While Addison's virtue and elegance embodied polite culture, he could also represent the other‐worldly and pious aspirations invoked by the Scriptures themselves.
Lewis Namier, Herbert Butterfield and Edmund Burke
Authors: SMYTH JAMES 
Published: September 2011

AbstractAlthough in respect of historical arguments, methodologies and prose style Herbert Butterfield and Lewis Namier were sharply contrasting (indeed antipathetic) historians, they had more in common that either would have chosen to admit. Paradoxically, those commonalities converged on the figure of Edmund Burke. For Namier, Burke was a political charlatan; Butterfield thought him ‘a mountain of a man’. Both nonetheless had distinctively Burkean conceptions of the limits – and dangers – of human rationality and of ‘organic’ change in the English past.
Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee
Authors: SINGH Kuljinder , SHARMA Rakesh , RAI Jaswant 
Published: September 2011

Abstract
Aim:  To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee.
Methods:  This is a prospective, double‐blind, placebo‐controlled and intention‐to‐treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake.
Results:  Of 84 patients screened, 74 patients formed the intent‐to‐treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 ± 5.07; WOMAC 15.9 ± 2.40) as compared to the placebo group (VAS 22.83 ± 6.90;WOMAC 36.8 ± 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 ± 5.16; WOMAC 16 ± 2.5) as compared to placebo group (VAS 33 ± 7.72; WOMAC 48.26 ± 3.5; P < 0.05), demonstrating the carry‐over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 ± 0.8087) as compared to the placebo group (12.433 ± 2.128; P < 0.05).
Conclusion:  Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee.
Introduction to the Special Issue: Governing Energy in a Fragmented World
Authors: Florini Ann , Dubash Navroz K. 
Published: September 2011

AbstractThis special issue brings together leading experts from Asia, Europe and North America to examine the international institutions, national governance mechanisms and financing systems that together will determine the future of the energy sector. The enormous environmental externalities imposed by fossil fuel extraction and consumption, the devastating corruption and human rights abuses that have accompanied this energy system, and the geopolitical vulnerabilities that have arisen because of the uneven natural distribution of these resources, have occasioned enormous handwringing – but not, yet, a shift to a more rational system of providing energy services. Although national governments play the dominant role in energy governance, these challenges are beyond the scope of any single national government to manage, making energy policy a key component of global governance and international relations.
40Ar‐39Ar and cosmic‐ray exposure ages of nakhlites—Nakhla, Lafayette, Governador Valadares—and Chassigny
Authors: KOROCHANTSEVA Ekaterina V. , SCHWENZER Susanne P. , BUIKIN Alexei I. , HOPP Jens , OTT Ulrich , TRIELOFF Mario 
Published: September 2011

Abstract– We present 40Ar‐39Ar dating results of handpicked mineral separates and whole‐rock samples of Nakhla, Lafayette, and Chassigny. Our data on Nakhla and Lafayette and recently reported ages for some nakhlites and Chassigny (Misawa et al. 2006; Park et al. 2009) point to formation ages of approximately 1.4 Ga rather than 1.3 Ga that is consistent with previous suggestions of close‐in‐time formation of nakhlites and Chassigny. In Lafayette mesostasis, we detected a secondary degassing event at approximately 1.1 Ga, which is not related to iddingsite formation. It may have been caused by a medium‐grade thermal event resetting the mesostasis age but not influencing the K‐Ar system of magmatic inclusions and the original igneous texture of this rock. Cosmic‐ray exposure ages for these meteorites and for Governador Valadares were calculated from bulk rock concentrations of cosmogenic nuclides 3He, 21Ne, and 38Ar. Individual results are similar to literature data. The considerable scatter of T3, T21, and T38 ages is due to systematic uncertainties related to bulk rock and target element chemistry, production rates, and shielding effects. This hampers efforts to better constrain the hypothesis of a single ejection event for all nakhlites and Chassigny from a confined Martian surface terrain (Eugster 2003; Garrison and Bogard 2005). Cosmic‐ray exposure ages from stepwise release age spectra using 38Ar and neutron induced 37Ar from Ca in irradiated samples can eliminate errors induced by bulk chemistry on production rates, although not from shielding conditions.
Population Pharmacokinetic/Pharmacogenetic Model for Optimization of Efavirenz Therapy in Caucasian HIV-Infected Patients
Authors: Sánchez Almudena , Cabrera Salvador , Santos Dolores , Valverde M. Paz , Fuertes Aurelio , Domínguez-Gil Alfonso , García María J. ,   the Tormes Group
Published: September 2011

ABSTRACTDespite extensive clinical experience with efavirenz (EFV), unpredictable interindividual variabilities in efficacy and toxicity remain important limitations associated with the use of this antiretroviral. The purpose of this study was to determine the factors affecting EFV pharmacokinetics and to develop a pharmacokinetic/pharmacogenetic (PK/PG) model in a Caucasian population of HIV-infected patients. In total, 869 EFV plasma concentrations from 128 HIV-infected patients treated with EFV were quantitatively assessed using a validated high-performance liquid chromatography technique. All patients were genotyped for 90 single nucleotide polymorphisms (SNPs) in genes coding for proteins involved in the metabolism and transport of EFV, using a MassArray platform provided by Sequenom. The influence of these polymorphisms on EFV pharmacokinetics and the effects of demographic, clinical, biochemical, lifestyle, and concurrent drug covariates were evaluated. Plasma concentrations were fitted by a one-compartment model, with first-order absorption and elimination using nonlinear mixed-effect modeling (NONMEM program). The CYP2B6*6 allele, multidrug resistance-associated protein 4 (MRP4) 1497C→T, and gamma-glutamyltranspeptidase (GGT) were identified as major factors influencing the apparent EFV oral clearance (CL/F), reducing the initial interindividual variability by 54.8%, according to the model CL/F = (12.2 − 0.00279·GGT)·0.602CYP2B6*6 [G/T]·0.354CYP2B6*6 [T/T]·0.793MRP4 1497C→T, where CYP2B6*6 [G/T], CYP2B6*6 [T/T], and MRP4 1497C→T take values of 0 or 1 to indicate the absence or presence of polymorphisms. The detailed genetic analysis conducted in this study identified two of 90 SNPs that significantly impacted CL/F, which might indicate that the remaining SNPs analyzed do not influence this PK parameter, at least in Caucasian populations with characteristics similar to those of our study population.
Analysis of the Functional Contributions of Asn233 in Metallo-β-Lactamase IMP-1
Authors: Brown Nicholas G. , Horton Lori B. , Huang Wanzhi , Vongpunsawad Sompong , Palzkill Timothy 
Published: September 2011

ABSTRACT

Metallo-β-lactamases, such as IMP-1, are a major global health threat, as they provide for bacterial resistance to a wide range of β-lactam antibiotics, including carbapenems. Understanding the molecular details of the enzymatic process and the sequence requirements for function are essential aids in overcoming β-lactamase-mediated resistance. An asparagine residue is conserved at position 233 in approximately 67% of all metallo-β-lactamases. Despite its conservation, the molecular basis of Asn233 function is poorly understood and remains controversial. It has previously been shown that mutations at this site exhibit context-dependent sequence requirements in that the importance of a given amino acid depends on the antibiotic being tested. To provide a more thorough examination as to the function and sequence requirements at this position, a collection of IMP-1 mutants encoding each of the 19 possible amino acid substitutions was generated. The resistance levels toward four β-lactam antibiotics were measured for
Escherichia coli
containing each of these mutants. The sequence requirements at position 233 for wild-type levels of resistance toward two cephalosporins were the most relaxed, while there were more stringent sequence requirements for resistance to ampicillin or imipenem. Enzyme kinetic analysis and determinations of steady-state protein levels indicated that the effects of the substitutions on resistance are due to changes in the kinetic parameters of the enzyme. Taken together, the results indicate that substitutions at position 233 significantly alter the kinetic parameters of the enzyme, but most substituted enzymes are able to provide for a high level of resistance to a broad range of β-lactams.
Enhanced Neutralization of HIV by Antibodies Displayed on the S-Layer of Caulobacter crescentus
Authors: Duval Mark , Lewis Christopher J. , Nomellini John F. , Horwitz Marc S. , Smit John , Cavacini Lisa A. 
Published: September 2011

ABSTRACT

Innovative methods of prevention are needed to stop the more than two million new HIV-1 infections annually, particularly in women. Local application of anti-HIV antibodies has been shown to be effective at preventing infection in nonhuman primates; however, the concentrations needed are cost prohibitive. Display of antibodies on a particulate platform will likely prolong effectiveness of these anti-HIV agents and lower the cost of goods. Here, we demonstrate that the bacterium
Caulobacter crescentus
and its highly expressed surface-layer (S-layer) protein can provide this antibody display platform. Caulobacters displaying protein G, alone or with CD4 codisplay, successfully captured HIV-1-specific antibodies and demonstrated functional neutralization. Compared to soluble antibodies, a neutralizing anti-HIV antibody displayed on
Caulobacter
was as effective or more effective at neutralizing diverse HIV-1 isolates. Moreover, when an antibody reactive with an epitope induced by CD4 binding (CD4i) was codisplayed with CD4, there was significant enhancement in HIV-1 neutralization. These results suggest that caulobacters displaying anti-HIV antibodies offer a distinct improvement in the use of antibodies as microbicides. Furthermore, these reagents can specifically evaluate anti-HIV antibodies in concert with other HIV-1 blocking agents to assess the most suitable tools for conversion to scFvs, allowing for direct display within the S-layer protein and further reducing cost of goods. In summary,
C. crescentus
, which can be easily produced and chemically stabilized at low cost, is well suited for engineering as an effective platform, offering an inexpensive way to produce and deliver HIV-1-specific microbicides.
Pharmacokinetics and Safety of Single-Dose Tenofovir Disoproxil Fumarate and Emtricitabine in HIV-1-Infected Pregnant Women and Their Infants
Authors: Flynn Patricia M. , Mirochnick Mark , Shapiro David E. , Bardeguez Arlene , Rodman John , Robbins Brian , Huang Sharon , Fiscus Susan A. , Van Rompay Koen K. A. , Rooney James F. , Kearney Brian , Mofenson Lynne M. , Watts D. Heather , Jean-Philippe Patrick , Heckman Barbara , Thorpe Edwin , Cotter Amanda , Purswani Murli ,   the PACTG 394 Study Team
Published: September 2011

ABSTRACT

Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section. Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth. All regimens were safe and well tolerated. Maternal areas under the serum concentration-time curve (AUC) and concentrations at the end of sampling after 24 h (
C
24
) were similar between the two doses of TDF; the maximum concentrations of the drugs in serum (
C
max
) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally (
P
= 0.04 and 0.046, respectively). The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median TFV concentration of 12 ng/ml 12 h after birth. Following administration of a single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their infants, 600 mg of TDF is acceptable as a single dose during labor. Low concentrations at birth support infant dosing as soon after birth as possible. Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression.
Griffithsin Has Antiviral Activity against Hepatitis C Virus
Authors: Meuleman Philip , Albecka Anna , Belouzard Sandrine , Vercauteren Koen , Verhoye Lieven , Wychowski Czeslaw , Leroux-Roels Geert , Palmer Kenneth E. , Dubuisson Jean 
Published: September 2011

ABSTRACT

Hepatitis C virus (HCV)-infected patients undergoing liver transplantation universally experience rapid reinfection of their new liver graft. Current treatment protocols do not prevent graft reinfection and, in addition, an accelerated disease progression is observed. In the present study, we have evaluated a novel strategy to prevent HCV infection using a lectin, griffithsin (GRFT) that specifically binds N-linked high-mannose oligosaccharides that are present on the viral envelope. The antiviral effect of GRFT was evaluated
in vitro
using the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems. We show here that preincubation of HCVpp and HCVcc with GRFT prevents infection of Huh-7 hepatoma cells. Furthermore, GRFT interferes with direct cell-to-cell transmission of HCV. GRFT acts at an early phase of the viral life cycle by interfering in a genotype-independent fashion with the interaction between the viral envelope proteins and the viral receptor CD81. The capacity of GRFT to prevent infection
in vivo
was evaluated using uPA
+/+
-SCID mice (uPA stands for urokinase-type plasminogen activator) that harbor human primary hepatocytes in their liver (chimeric mice). In this proof-of-concept trial, we demonstrated that GRFT can mitigate HCV infection of chimeric mice. Treated animals that did become infected demonstrated a considerable delay in the kinetics of the viral infection. Our data demonstrate that GRFT can prevent HCV infection
in vitro
and mitigate HCV infection
in vivo
. GRFT treatment of chronically infected HCV patients undergoing liver transplantation may be a suitable strategy to prevent infection of the liver allograft.
TMC310911, a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor, Shows
In Vitro
an Improved Resistance Profile and Higher Genetic Barrier to Resistance Compared with Current Protease Inhibitors
Authors: Dierynck Inge , Van Marck Herwig , Van Ginderen Marcia , Jonckers Tim H. M. , Nalam Madhavi N. L. , Schiffer Celia A. , Raoof Araz , Kraus Guenter , Picchio Gaston 
Published: September 2011

ABSTRACT

TMC310911 is a novel human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) structurally closely related to darunavir (DRV) but with improved virological characteristics. TMC310911 has potent activity against wild-type (WT) HIV-1 (median 50% effective concentration [EC
50
], 14 nM) and a wide spectrum of recombinant HIV-1 clinical isolates, including multiple-PI-resistant strains with decreased susceptibility to currently approved PIs (fold change [FC] in EC
50
, >10). For a panel of 2,011 recombinant clinical isolates with decreased susceptibility to at least one of the currently approved PIs, the FC in TMC310911 EC
50
was ≤4 for 82% of isolates and ≤10 for 96% of isolates. The FC in TMC310911 EC
50
was ≤4 and ≤10 for 72% and 94% of isolates with decreased susceptibility to DRV, respectively.
In vitro
resistance selection (IVRS) experiments with WT virus and TMC310911 selected for mutations R41G or R41E, but selection of resistant virus required a longer time than IVRS performed with WT virus and DRV. IVRS performed with r13025, a multiple-PI-resistant recombinant clinical isolate, and TMC310911 selected for mutations L10F, I47V, and L90M (FC in TMC310911 EC
50
= 16). IVRS performed with r13025 in the presence of DRV required less time and resulted in more PI resistance-associated mutations (V32I, I50V, G73S, L76V, and V82I; FC in DRV EC
50
= 258). The activity against a comprehensive panel of PI-resistant mutants and the limited
in vitro
selection of resistant viruses under drug pressure suggest that TMC310911 represents a potential drug candidate for the management of HIV-1 infection for a broad range of patients, including those with multiple PI resistance.
Development of Dual-Acting Pyrimidinediones as Novel and Highly Potent Topical Anti-HIV Microbicides
Authors: Watson Buckheit Karen , Yang Lu , Buckheit Robert W. 
Published: September 2011

ABSTRACT

In the absence of an effective vaccine against the human immunodeficiency virus (HIV), topical microbicides to prevent the sexual transmission of HIV represent an important strategy to prevent the continued spread of infection. The recent trend in the development of new microbicide candidates includes the utilization of FDA-approved therapeutic drugs that target the early stages of the HIV life cycle, including entry inhibitors and reverse transcriptase inhibitors. We have investigated 12 pyrimidinedione compounds with potent HIV activities and their abilities to inhibit both virus entry and reverse transcription, in an effort to determine a lead microbicide for product development. The candidate compounds were evaluated for efficacy against subtype B, C, and E clinical virus strains in fresh human peripheral blood mononuclear cells and against CCR5-tropic virus strains in both monocyte-macrophages and dendritic cells. Microbicide-specific biological assays and toxicity evaluations were also performed in a variety of established and fresh human cells as well as against
Lactobacillus
strains common to the vaginal environment. These evaluations resulted in the identification of congeners with cyclopropyl and cyclobutyl substituents at the N-1 of the pyrimidinedione as the most active molecules in the structure-activity relationship series. The pyrimidinediones represent excellent microbicide candidates in light of their significantly high efficacies against HIV-1 (subnanomolar concentration range), potencies (therapeutic index, >1 million), solubility profiles, and dual mechanism of antiviral action that includes two early steps of virus replication prior to the integration of the virus that are considered most important for microbicidal activity.
Helicobacter pylori Resistance to Rifabutin in the Last 7 Years
Authors: Nishizawa Toshihiro , Suzuki Hidekazu , Matsuzaki Juntaro , Muraoka Hiroe , Tsugawa Hitoshi , Hirata Kenro , Hibi Toshifumi 
Published: September 2011

ABSTRACT

A low rate of resistance (0.24%) to rifabutin was noted in
Helicobacter pylori
strains isolated from 414 Japanese patients. The only rifabutin-resistant strain detected showed a point mutation in the
rpoB
gene and was isolated from a patient with a history of rifampin treatment for pulmonary tuberculosis.
Antimicrobial Actions of Reactive Oxygen Species
Authors: Fang Ferric C. 
Published: September 2011

ABSTRACT

Everything should be as simple as it can be, but not simpler.

—Attributed to Albert Einstein (1)

IMPORTANCE
Reactive oxygen species (ROS) are produced by host phagocytes and exert antimicrobial actions against a broad range of pathogens. The observable antimicrobial actions of ROS are highly dependent on experimental conditions. This perspective reviews recent controversies regarding ROS in
Salmonella
-phagocyte interactions and attempts to reconcile conflicting observations from different laboratories.