OH-Cbl is not part of the product manufacturing process; however

OH-Cbl is not part of the product manufacturing process; however we found cyanocobalamin (CN-Cbl) in cell culture media converts to OH-Cbl in the presence of light. OH-Cbl can be released from mAb and Fc-fusion proteins by conversion with potassium

cyanide to CN-Cbl, which does selleck products not bind. By exploiting the differential binding of CN-Cbl and OH-Cbl, we developed a rapid and specific assay to accurately measure B-12 levels in purified protein. Analysis of multiple products and lots using this technique gives insight into color variability during manufacturing.”
“This paper presents an uncomplicated high-yield fabrication process for creating large-scale integrated (LSI) 3-D 123 microfluidic networks in poly(dimethylsiloxane) (PDMS). The key innovation lays in the robust definition of miniaturized out-of-plane fluidic interconnecting channels

(=vias) between stacked layers of microfluidic channels in standard PDMS. Unblocked vias are essential for creating 3-D microfluidic networks. Previous methods either suffered find more from limited yield in achieving unblocked vias due to residual membranes obstructing the vias after polymerization, or required complicated and/or manual procedures to remove the blocking membranes. In contrast, our method prevents the formation of residual membranes by inhibiting the PDMS polymerization on top of the mold features that define the vias. In addition to providing unblocked vias, the inhibition process also leaves a partially cured, sticky flat-top surface that adheres well to other surfaces and that allows self-sealing stacking of several PDMS layers. We demonstrate the new method by manufacturing a densely perforated PDMS membrane and an LSI 3-D PDMS microfluidic channel network. We also characterize the inhibition mechanism and study the critical process parameters. We demonstrate that the method is suitable for structuring PDMS layers with a thickness down to 10 mu m.”
“This study, conducted within

a larger participatory action research project, explored satisfaction with end-of-life care among African Americans in a rural southeastern community. Researchers collaborated with practitioners Epigenetic signaling inhibitors and the African American community, conducting qualitative interviews with 1 African American hospice patient, 9 primary caregivers of terminally ill patients within hospice, and 10 family caregivers outside of hospice. Results indicated a more positive experience for hospice patients, and that most nonhospice participants preferred hospice after learning about it through the study. Participants made recommendations for public information efforts, the referral and intake process, and developing a relationship with the African American community.

Mean EPO concentration was 62% higher for HF subjects with CSA th

Mean EPO concentration was 62% higher for HF subjects with CSA than for healthy controls (P = 0.004). The magnitude of nocturnal hypoxaemia was significantly and positively

related to EPO concentration (r = 0.45, P = 0.02). Advanced HF was also significantly and positively related Anlotinib clinical trial to EPO concentration (r = 0.43, P = 0.02). On multivariate analysis, the presence of combined nocturnal hypoxaemia and advanced HF yielded greater correlation to EPO concentration than either factor alone (r = 0.57, P = 0.04 and P = 0.05, respectively). Linear regression demonstrated that the combination of New York Heart Association Class and CSA was strongly associated with EPO concentration (P < 0.0001).\n\nConclusion In non-anaemic HF patients, advanced HF and hypoxaemia due to CSA may each be independently associated with increased serum EPO concentration.”
“Patients with temporal lobe seizures sometimes experience what John Hughlings Jackson described

as “dreamy states” during seizure onset. These phenomena may be characterized by a re-experiencing of past events, feelings of familiarity (deja vu), and hallucinations. In previous reports, patients have been aware of the illusory nature of their experiences. Here, however, the case of a patient with a documented 37-year history of temporal lobe epilepsy who is not aware is described. Fifteen years ago, the patient saw visions of traumatic autobiographical events that he had never previously recalled. He believed them to be veridical memories from his childhood, although evidence from his family suggests selleck chemical that they were not. The patient’s psychological reaction to the “recovery” of these traumatic “memories” was severe enough to qualify as posttraumatic stress disorder (PTSD). To our knowledge, this is the first report of PTSD caused by the misattribution of mental states that accompany a seizure. (C) 2010 Elsevier Inc. All rights reserved.”
“Surprisingly, a high frequency of interspecific

sea turtle hybrids has been previously recorded in a nesting site along a short stretch of the Brazilian coast. Mitochondrial DNA data indicated that as much as 43% of the females identified as Eretmochelys imbricata are hybrids in this area (Bahia State of Brazil). It is a remarkable find, because most of the nesting sites surveyed worldwide, including some in northern Brazil, presents R406 mw no hybrids, and rare Caribbean sites present no more than 2% of hybrids. Thus, a detailed understanding of the hybridization process is needed to evaluate natural or anthropogenic causes of this regional phenomenon in Brazil, which could be an important factor affecting the conservation of this population. We analysed a set of 12 nuclear markers to investigate the pattern of hybridization involving three species of sea turtles: hawksbill (E. imbricata), loggerhead (Caretta caretta) and olive ridley (Lepidochelys olivacea). Our data indicate that most of the 432 individuals in the crossings L. olivacea x E.

In the initial wear-in period, grains pull-out caused by grain-bo

In the initial wear-in period, grains pull-out caused by grain-boundary microcracking is the dominant wear mechanism of submicron grained alumina. In the case of alumina of large grain size, intergranular and transgranular fracture is the basic wear mechanism. As the sliding time increases, compaction of wear debris on sliding surface of fine and coarsen alumina determines the wear characteristics.”
“This study investigates how familiarity and initial contact with species can be explained by social-demographic

variables in an arid environment of Argentina. Our main objectives were to investigate which species children are familiar with, and analyse the effect of place of residence, sex and age on students’ knowledge and initial

this website contact with species. In total, 1746 students between 7 and 18 years old participated in the study, from 25 urban and 19 rural schools. Students were asked to write down ten animals and ten SN-38 datasheet plants, and to indicate where they had seen them for the first time. Children were able to name an important number of species but they were mostly acquainted with exotic ones. Familiarity with species and the use of different sources of information can be explained by interactions between the studied factors, while place of residence was not as significant as we expected. Sex was an important explanatory variable, likely influenced by differences in roles and children activities’ preferences. It is necessary to improve the knowledge on native species, particularly those with conservation problems by using information learn more sources close to nature, without neglecting the knowledge of the exotic species that children showed more familiarity from everyday life. (C) 2012 Elsevier Ltd. All rights reserved.”
“The proposition “This house agrees that the proper study of man is woman” was debated. For those negating the proposition, the alternative was that “animal models are useful in understanding the human feto-maternal relationship.” Evidence for the proposition emphasized molecular and structural differences between the human and animal placenta and placentation.

Evidence against the proposition and in favor of the alternative focused on functional and structural homologies, emphasizing that different molecules could be used in humans to achieve similar functional effects seen in animal (e.g., mouse) models. It was agreed that one always needed to test the validity of animal data by studying humans. The advantages and limitations of animal models were discussed. (C) 2014 Elsevier Ireland Ltd. All rights reserved.”
“Cadherins are cell surface adhesion proteins important for tissue development and integrity. Type I and type II, or classical, cadherins form adhesive dimers via an interface formed through the exchange, or ” swapping ”, of the N-terminal beta-strands from their membrane-distal EC1 domains.

This regulation is mainly related to altered associations between

This regulation is mainly related to altered associations between membrane skeletal

proteins and integral proteins, with the latter serving to anchor the skeleton to the lipid matrix. It has been hypothesized that shear stress induces alterations of RBC deformability: the current study investigated the dynamics of the transient improvement in deformability induced by shear stress at physiologically-relevant levels. RBC were exposed to various levels of shear stress (SS) in a Couette type shearing system that is part of an ektacytometer, thus permitting the changes in RBC deformability during the NCT-501 clinical trial application of SS to be monitored. Initial studies showed that there is an increase in deformability of the RBC subjected to SS in selleck the range of 5-20 Pa, with kinetics characterized by time constants of a few seconds. Such improvement in deformability, expressed by an elongation index (EI), was faster with higher levels of SS and hence yielded shorter time constants: absolute values of EI increased by 3-8% of the starting level. Upon the removal of the

shear stress, this response by RBC was reversible with a slower time course compared to the increase in EI during application of SS. Increased calcium concentration in the RBC suspending medium prevented the improvement of deformability. It is suggested that the improvement of RBC deformability by shear forces may have significant effects on blood flow dynamics, at least in tissues supplied by blood vessels with impaired

vasomotor reserve, and may therefore serve as a compensating mechanism for the maintenance of adequate microcirculatory perfusion.”
“Background: Pathological left ventricular (LV) hypertrophy frequently progresses to dilated heart failure with suppressed mitochondrial oxidative capacity. Dietary marine omega-3 polyunsaturated fatty acids (omega-3 PUFA) up-regulate adiponectin and prevent LV dilation in rats subjected to pressure overload. This study 1) assessed the effects of omega-3 PUFA on LV dilation and down-regulation of mitochondrial enzymes in response to pressure overload; and 2) evaluated the role of adiponectin in mediating the effects of omega-3 PUFA in heart.\n\nMethods: Wild type INCB024360 chemical structure (WT) and adiponectin-/- mice underwent transverse aortic constriction (TAC) and were fed standard chow +/- omega-3 PUFA for 6 weeks. At 6 weeks, echocardiography was performed to assess LV function, mice were terminated, and mitochondrial enzyme activities were evaluated.\n\nResults: TAC induced similar pathological LV hypertrophy compared to sham mice in both strains on both diets. In WT mice TAC increased LV systolic and diastolic volumes and reduced mitochondrial enzyme activities, which were attenuated by omega-3 PUFA without increasing adiponectin.

The results

The results EVP4593 molecular weight of this study support the previous findings that P. zopfii may resist high-temperature treatments, including

that applied in the high-temperature, short-time (HTST) pasteurization process. The obtained data also demonstrate the efficacy of the three classes of teat disinfectants against P. zopfii, with the efficacy of iodine being most pronounced. The study emphasizes the necessity of using higher temperatures in the pasteurization of raw milk to kill the Prototheca algae, as well as the particular suitability of the iodine for the control procedures of protothecal mastitis.”
“SnS2/TiO2 nanocomposites with adjustable TiO2 contents were synthesized directly via the solvothermal reactions of SnCl4 center dot 5H(2)O, thioacetamide and different amounts of tetrabutyl titanate in the mixed solvents of ethanol and acetic acid at 180 degrees C for 12 h. The structures, compositions, Brunauer-Emmett-Teller (BET) specific surface areas and optical properties of the as-synthesized products were characterized by X-ray diffraction, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, Fer-1 field emission scanning electron microscopy, high resolution transmission electron microscopy, N-2 adsorption and UV-vis diffuse reflectance

spectra, and their photocatalytic properties were tested for the reduction of aqueous Cr(VI) under visible light (lambda > 420 nm) irradiation. Furthermore, contrast photocatalytic experiments were also conducted for different doses of the as-synthesized SnS2/TiO2 nanocomposite, SnS2 and physical mixture of SnS2 and TiO2. It was found that the as-synthesized SnS2/TiO2 nanocomposite with a suitable TiO2 content (e.g., 44.5 mass% TiO2) not only exhibited extraordinary superior photocatalytic activity to SnS2,

TiO2 and physical mixture of SnS2 and TiO2 (44.5 mass%) at different catalyst doses, but also had good photocatalytic selleck screening library stability. Moreover, Cr(VI) can be reduced to Cr(III) by SnS2/TiO2-mediated photocatalysis. The tight heterojunction structure of the as-synthesized SnS2/TiO2 nanocomposite, which can facilitate interfacial electron transfer and reduce the separation and self-agglomeration of two components, was considered to play an important role in achieving its greatly improved photocatalytic performance. (c) 2012 Elsevier B.V. All rights reserved.”
“Background: Being physically inactive has been linked to a higher mortality and poorer quality of life. This cross-sectional study examines the prevalence of leisure-time sedentary behaviour in a population of Spanish adults and its correlates with several sociodemographic variables. Methods: Data were collected from 1,330 subjects living in Madrid (age: 18-65 years, 51.6% women) by telephone interview. The sampling error was +/- 2.7% for a 95.5% confidence level. Leisure-time sedentary behaviour was assessed using the Global Physical Activity Questionnaire (version 2).

Objective: To assess the relationship between cord blood 25-h

\n\nObjective: To assess the relationship between cord blood 25-hydroxyvitamin

D (25[OH]D) levels and allergic outcomes through age 5 years.\n\nMethods: Cord blood 25(OH)D levels were measured in 219 participants in the Tucson Infant Immune Study, a population-based birth cohort. Plasma total IgE and specific IgE levels to 6 aeroallergens were measured at 1, 2, 3, and 5 years. Skin prick test (SPT) positivity (wheal diameter >= 3 mm) and physician-diagnosed active allergic rhinitis and asthma were assessed at age 5 years. Longitudinal models were used to assess the relationship between 25(OH)D and IgE levels. Logistic regression models were used to assess the relationship of 25(OH)D level with SPT positivity, allergic see more rhinitis, and asthma.\n\nResults: The median cord blood 25(OH)D level was 64 nmol/L (interquartile range, VX-809 49-81

nmol/L). Relative to the reference group (50-74.9 nmol/L), both low (<50 nmol/L) and high (>= 100 nmol/L) levels were associated with increased total IgE (coefficient = 0.27, P = .006 and coefficient = 0.27, P = .04, respectively) and detectable inhalant allergen-specific IgE (odds ratio = 2.4, P = .03 and odds ratio = 4.0, P = .01, respectively) through age 5 years. High 25(OH)D levels were also associated with increased SPT positivity (odds ratio = 4.0, P = .02). By contrast, the 25(OH)D level was not significantly associated with allergic rhinitis or asthma.\n\nConclusion: Both low and high levels of cord blood 25(OH)D were associated with increased aeroallergen sensitization. The association between vitamin D status and actual allergic diseases merits further study. (J Allergy

Clin Immunol FG-4592 inhibitor 2011;128:1093-9.)”
“OBJECTIVES. Rotavirus is the leading cause of acute gastroenteritis requiring hospitalization in young children. Data on the burden of rotavirus gastroenteritis are needed to guide recommendations for rotavirus vaccine use. This study was undertaken to estimate the burden of rotavirus gastroenteritis in European children <5 years of age.\n\nMETHODS. This prospective, study was conducted in 12 hospitals in France, Germany, Italy, Spain, and the United Kingdom. A sample of all children aged <5 years presenting to emergency departments or hospitalized because of community-acquired acute gastroenteritis was enrolled for parental interview and stool collection. Acute gastroenteritis was defined as diarrhea (>= 3 loose stools per 24 hours) for <14 days. Rotavirus was detected by enzyme-linked immunosorbent assay and typed by reverse-transcriptase polymerase chain reaction.\n\nRESULTS. Between February 2005 and August 2006, 3734 children with community-acquired acute gastroenteritis were recruited and retained for analysis (55.9% via the emergency department, 41.8% hospitalized). Of the 2928 community-acquired acute gastroenteritis cases for which stool samples were available, 43.4% were rotavirus-positive by enzyme-linked immunosorbent assay (32.

Patients and methods: We assessed 68 shoulders in 66 patients

\n\nPatients and methods: We assessed 68 shoulders in 66 patients (36 women and 30 men) with a mean age of 66 years (range, 53-84 years), first preoperatively and then at a minimum click here of 2 years’ follow-up, using the Constant score for pain; Constant Shoulder Score; Oxford Shoulder Score; University of California, Los Angeles shoulder rating scale; and Disabilities of the Arm, Shoulder and Hand score. Any complications were assessed according to Goslings and Gouma.\n\nResults: We report statistically significant improvements of all obtained scores at a mean follow-up of 42 months (range, 24-96 months) in both groups. Significant outcome differences between 29

patients with previous shoulder arthroscopy for cuff tear reconstruction and 39 patients without previous shoulder arthroscopy were not observed. In total, 8 complications occurred: 1 nerve lesion, 3 cases of loosening of the humeral stem, and 4 cases of luxation of the glenoid component.\n\nConclusion: We conclude that reverse total shoulder arthroplasty with the Delta prosthesis is significantly beneficial in terms of less shoulder pain, greater stability, and gain in range of motion without this beneficial effect being significantly weakened by previous insufficient shoulder arthroscopy for cuff find more tear reconstruction. We believe that

previous arthroscopic cuff tear reconstruction should therefore be included

in the treatment algorithm.\n\nLevel of evidence: Level III, Case-Control Study, Treatment Study. (C) 2011 Journal of Shoulder and Elbow Surgery Board of Trustees.”
“The quantitative determination of volatile compounds of Chardonnay wines using HS-SPME-GC x GC/TOFMS along with the determination of odor activity value (OAV) and relative odor contribution (ROC) of volatiles SHP099 concentration are reported for the first time. The use of GC x GC/TOFMS for the analysis of Chardonnay wine of Serra Gaucha resulted in the tentative identification of 243 compounds, showing the superior performance of this analytical technique for this specific varietal wine, considering that the number of compounds usually separated by 1D-GC for this type of wine is lower. Furthermore, 42 compounds co-eluted in the first dimension and 34 of them were separated in the second dimension, while the others were resolved by spectral deconvolution (8), which indicates that the conventional 1D-GC/MS may result in misleading results. The calculation of OAV and ROC allowed the determination of the volatile compounds that presented the greater contribution to wine aroma. Ethyl octanoate, ethyl hexanoate, ethyl butanoate, and beta-damascenone showed the highest OAV and ROC values, although other 43 compounds showed also potential to contribute to wine aroma. Figures of merit of the developed method were: accuracies from 92.4 to 102.

During follow-up, all events occurring between two visits, in par

During follow-up, all events occurring between two visits, in particular hospital admissions or nursing home placements were carefully recorded. Results: Annual incidences for hospitalizations were 26.2% (95% CI, 22.5 to 29.7). After two years, 202 subjects were hospitalized for 296 hospitalizations. 139 subjects were hospitalized once, 40 twice, 13 three times, 4 four times and 2 five WH-4-023 research buy times during the two-year follow-up. The

duration of hospitalization was 14.3 +/- 23.5 days. For repeated hospitalizations, the time interval between the first and the second hospitalization was 176.4 days (SD 150.2) and the cause of multiple hospitalizations was most different. Fractures and falls not causing fracture were the main reasons for hospital admission (20.9%), followed by P5091 clinical trial cardiovascular disorders (14.5%) and by behavioural disorders (11.0%). Admission due to associated diseases or life events was the main reason for hospitalization (75.7%). Conclusions: Hospitalization is a frequent event for AD patients even at mild to moderate stage of the disease. In this cohort, the major causes for hospital admission were due to associated

diseases or life events and not due to the direct consequences of the disease itself.”
“Retained placenta is one of the most common peripartum complications in mares. It delays the recovery of the uterus, decreases fertility, and can be life-threatening. The mechanism of normal placenta release is unknown. In addition to systemic hormonal changes affecting the process of placenta separation, it is supposed that local mechanisms at the cellular level may play an important role in this process. It is known that the incidence of retained placenta correlates with reduced

expression of classic class I major histocompatibility complex protein (classic MHC I) in cows’ placentas. In mares, classic MHC I is expressed in early pregnancy, but it is unknown if classic MHC I is expressed again check details in peripartum and if reduced expression correlates with retained placenta in mares. Both early and late expression seem likely, because early expression would prepare mares to reject placenta tissues if MHC is expressed peripartum. This article discusses how MHC I is expressed in placental tissues; how it affects lymphocyte migration, metalloproteinase activation, and extra-cellular matrix remodelling in those tissues; and how various factors can affect MHC I activation. The paper also describes a hypothesis for the mechanism of placenta separation in mares based on the similarity of these processes in other species that have been more extensively studied.”
“There is no published literature detailing the demographics of paediatric amputations in the United Kingdom. We performed this review of children and adolescents referred to a regional limb-fitting centre from the 1930s to the current decade who suffered amputation as a result of trauma, and compared our data with similar cohorts from other units.

Here, we summarise the evidence for involvement of specific tyros

Here, we summarise the evidence for involvement of specific tyrosine kinases in the pathogenesis of IPF and the development of

tyrosine kinase inhibitors as treatments for IPF.”
“To date, the signal transducing adaptor molecule 2 (STAM2) was shown to harbour two ubiquitin binding domains (UBDs) known as the VHS and UIM domains, while the SH3 domain of STAM2 was reported to interact with deubiquitinating enzymes (DUBs) like UBPY and AMSH. In the present study, NMR evidences the interaction of the STAM2 SH3 domain with ubiquitin, demonstrating that SH3 constitutes the third UBD of STAM2. Furthermore, we show that a UBPY-derived peptide can outcompete ubiquitin for SH3 binding and vice versa. These results suggest that the SH3 domain Fer-1 chemical structure of STAM2 plays versatile roles in the context of ubiquitin mediated receptor sorting. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.”
“Maternal fish intake during pregnancy may influence the risk of child asthma and allergic rhinitis, yet evidence is conflicting on its association with

these outcomes. We examined the associations of maternal fish intake during MDV3100 in vivo pregnancy with child asthma and allergic rhinitis. Mothers in the Danish National Birth Cohort (n 28 936) reported their fish intake at 12 and 30 weeks of gestation. Using multivariate logistic regression, we examined the associations of fish intake with child wheeze, asthma and rhinitis assessed at several time points: ever wheeze, recurrent wheeze (>3 episodes), ever asthma and allergic rhinitis, and current asthma, assessed at 18 months (n approximately 22 000) and 7 years (n approximately 17 000) using self-report and registry data on hospitalisations and prescribed medications. Compared with consistently high fish intake during pregnancy (fish as a sandwich or hot meal >= 2-3 times/week), never eating fish was associated with a higher risk of child asthma diagnosis at 18 months (OR 1.30, 95% CI 1.05, 1.63, P = 0.02), and ever asthma

by hospitalisation (OR 1.46, 95% CI 0.99, 2.13, P = 0.05) and medication prescription (OR 1.37, 95% Dinaciclib manufacturer CI 1.10, 1.71, P = 0.01). A dose-response was present for asthma at 18 months only (P for trend 0.001). We found no associations with wheeze or recurrent wheeze at 18 months or with allergic rhinitis. The results suggest that high (v. no) maternal fish intake during pregnancy is protective against both early and ever asthma in 7-year-old children.”
“To evaluate roles of preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast cancer patients.\n\nFive hundred and sixty-five consecutive breast cancer patients were prospectively randomized into groups with or without preoperative lymphoscintigraphy.\n\nIn a group with lymphoscintigraphy, 238 patients had sentinel lymph nodes spotted in lymphoscintigram.

Our results showed that progressive miR-221 downregulation hallma

Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa.”
“Quantitative Structure-Activity/Property Relationships (QSAR/QSPR) models have been largely used for different kind of problems in Selleckchem GSK1210151A Medicinal Chemistry and other Biosciences as well. Nevertheless, the applications of QSAR models have been restricted to the study of small molecules in the past. In this context, many authors use molecular graphs, atoms (nodes) connected by chemical bonds (links) to represent and numerically characterize

the molecular structure. On the other hand, Complex Networks are useful in solving problems in drug research and industry, developing mathematical representations of different systems. These systems move in a wide range from relatively simple graph representations of drug molecular structures (molecular graphs used in classic QSAR) to large systems. We can cite for instance, drug-target interaction networks, protein structure networks, protein interaction networks (PINs), or drug treatment in large geographical disease spreading

networks. In any case, all complex networks have essentially the same components: nodes (atoms, drugs, proteins, microorganisms and/or parasites, geographical areas, drug policy legislations, etc.) and links (chemical bonds, drug-target interactions, drug-parasite treatment, drug use, etc.). selleck screening library Consequently, we can use the same type of numeric FK228 order parameters called Topological Indices (TIs) to describe the connectivity patterns in all these kinds of Complex Networks irrespective the nature of the object they represent and use these TIs to develop QSAR/QSPR models beyond the classic frontiers of drugs small-sized molecules. The goal of this work, in first instance, is to offer a common background to all the manuscripts presented in this special issue. In so doing, we make a review of the most used software and databases, common types of QSAR/QSPR models, and complex networks

involving drugs or their targets. In addition, we review both classic TIs that have been used to describe the molecular structure of drugs and/or larger complex networks. In second instance, we use for the first time a Markov chain model to generalize Spectral moments to higher order analogues coined here as the Stochastic Spectral Moments TIs of order k (pi(k)). Lastly, we report for the first time different QSAR/QSPR models for different classes of networks found in drug research, nature, technology, and social-legal sciences using pi(k) values. This work updates our previous reviews Gonzalez-Diaz et al. Curr Top Med Chem. 2007; 7(10): 1015-29 and Gonzalez-Diaz et al. Curr Top Med Chem. 2008; 8(18):1676-90.