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Search Results: 1 - 10 of 464581 matches for " Lawrence A. Kingsley "
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Fat distribution and longitudinal anthropometric changes in HIV-infected men with and without clinical evidence of lipodystrophy and HIV-uninfected controls: A substudy of the Multicenter AIDS Cohort Study
Todd T Brown, Xiaoqiang Xu, Majnu John, Jaya Singh, Lawrence A Kingsley, Frank J Palella, Mallory D Witt, Joseph B Margolick, Adrian S Dobs
AIDS Research and Therapy , 2009, DOI: 10.1186/1742-6405-6-8
Abstract: Between 1999 and 2002, 33 men with clinical evidence of lipodystrophy (LIPO+), 23 HIV-infected men without clinical evidence of lipodytrophy (LIPO-), and 33 HIV-uninfected men were recruited from the four sites of the Multicenter AIDS Cohort Study (MACS). Participants underwent dual-energy x-ray absorptiometry, quantitative computerized tomography of the abdomen and thigh, and circumference measurements of the waist, hip and thigh. Circumference measurements at each semi-annual MACS visit between recruitment and 2008 were used to compare average annual anthropometric changes in the 3 groups.Body mass index (BMI) was lower in LIPO+ men than in the LIPO- men and the HIV- uninfected controls (BMI: 23.6 ± 0.4 vs 26.8 ± 1.5 vs 28.7 ± 0.9 kg/m2, respectively, p < 0.001). The average amount of visceral adipose tissue (VAT) was similar in all three groups (p = 0.26), but after adjustment for BMI, VAT was higher in the LIPO+ group (169 ± 10 cm2) compared to the LIPO- men (129 ± 12 cm2, p = 0.03) and the HIV-uninfected group (133 ± 11 cm2, p = 0.07). Subcutaneous adipose tissue (thigh, abdomen) and total extremity fat were less in the HIV-infected men (LIPO+ and LIPO-) than in the HIV-uninfected men. Over an average of 6 years of follow-up, waist circumference increased at a faster rate in LIPO+ group, compared to the LIPO- men (0.51 cm/year vs 0.08 cm/year, p = 0.02) and HIV-uninfected control men (0.21 cm/year, p = 0.06). The annual changes in hip and thigh circumferences were similar in all three groupsSubcutaneous lipoatrophy was observed in HIV-infected patients, even those without clinical evidence of lipodystrophy, compared to age-matched HIV-uninfected men. Despite markedly lower BMI, HIV-infected men with lipodystrophy had a similar amount of VAT as HIV-uninfected men and tended to have more rapid increases in waist circumference over 6 years of follow-up. These longitudinal increases in waist circumference may contribute to the development of cardiovascular risk in
Factors Affecting Glomerular Filtration Rate, as Measured by Iohexol Disappearance, in Men with or at Risk for HIV Infection
Joseph B. Margolick, Lisa P. Jacobson, George J. Schwartz, Alison G. Abraham, Annie T. Darilay, Lawrence A. Kingsley, Mallory D. Witt, Frank J. Palella
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086311
Abstract: Objective Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD). Design Cross-sectional measurement of iohexol-based GFR (iGFR) in HIV(+) men (n = 455) receiving antiretroviral therapy, and HIV-uninfected (HIV(?)) men (n = 258) in the Multicenter AIDS Cohort Study. Methods iGFR was calculated from disappearance of infused iohexol from plasma. Determinants of GFR and the presence of CKD were compared using iGFR and GFR estimated by the CKD-Epi equation (eGFR). Results Median iGFR was higher among HIV(+) than HIV(?) men (109 vs. 106 ml/min/1.73 m2, respectively, p = .046), and was 7 ml/min higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR (≤90 ml/min/1.73 m2) was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. CKD was more common in HIV(+) than HIV(?) men; predictors of CKD were similar using iGFR and eGFR. Conclusions iGFR was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men. Presence of CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR.
Circulating Mediators of Inflammation and Immune Activation in AIDS-Related Non-Hodgkin Lymphoma
Brian M. Nolen, Elizabeth Crabb Breen, Jay H. Bream, Frank J. Jenkins, Lawrence A. Kingsley, Charles R. Rinaldo, Anna E. Lokshin
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099144
Abstract: Background Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed bead-based immunoassays. Results A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease.
Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression
Sher L. Hendrickson,James A. Lautenberger,Leslie Wei Chinn,Michael Malasky,Efe Sezgin,Lawrence A. Kingsley,James J. Goedert,Gregory D. Kirk,Edward D. Gomperts,Susan P. Buchbinder,Jennifer L. Troyer,Stephen J. O'Brien
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012862
Abstract: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.
Utopianism and the New World Order: A Critical Consideration  [PDF]
Okoro Kingsley
Open Journal of Philosophy (OJPP) , 2014, DOI: 10.4236/ojpp.2014.43037
Abstract: Utopianism, which has been inveigled in various circles into epistemological obscurity, has been the force behind several socio-political and economic reforms of many generations. Scholars accredit religious thoughts as the purveyor of the messianic utopianism, while classical utopianism is accredited to Plato and Aristotle. However,Thomas Moore coined the word utopia and furthered the concept in the modern times. Overly, the power of utopian thinking lies in the strength of imaginative thought. Thus utopianism is christened idealism and dismissed as irrelevant to real life experiences of the modern man. However, the works of Thomas Moore, on the contrary, have thrown hindsight to the fact that utopian thoughts are relevant both for the spiritual and material worlds. Here, utopian thinking serves as a critique to the ineptitude of the utopianist’s society. Utopia becomes a means of addressing the evils of the society in which the utopian lives(d). In the works of Thomas Moore, the imaginary city of utopia becomes an ideal state, where all the citizens live in peace and harmony, contrary to the European society of Moore’s time, where oppression, war and social disorder were the dicta. Against this backdrop, this paper found epistemological connection between Moore’s period and the contemporary period and decided to apply Moore’s utopian thoughts to the modern times. It concludes that if Moore’s utopianism is applied with modification, the present world will attain its dream of becoming a common community, which extols friendship and brotherhood.
Islamic Jurisprudence and Unity of Nigeria: A Socio-Historical Reconsideration  [PDF]
Kingsley Okoro
Open Journal of Philosophy (OJPP) , 2017, DOI: 10.4236/ojpp.2017.74025
Abstract: Nigeria’s journey into nationhood has been steely as it has encountered several horrendous setbacks. The journey started with the amalgamation of 1914. Since then, the uniting groups have engaged themselves in competition for dominance, instead of dialoguing for true unity/union which is necessary for nation building. This has resulted in internecine wars, conflict and crises, in several reins of the country’s life. However with more than one hundred years of this marriage, it is therefore necessary to recast our journey. In recasting this history, we shall call to mind that: 1) The Nigeria foremost nationalists dreamt and laboured to make this country a great nation; 2) it is in the quest for this unity that the civil war of 1967-70 was fought; 3) Nigeria is founded on secularity/secular state ideality. Therefore, it is now time to redefine the basis for this unity, noting that great nations have heterogeneous formations, suggesting that our heterogeneity is not truly a weakness to our nation building goal. Therefore, to hide under the ambit of religion or ethnic myopism to scuttle the labours of our heroes past can never stand the test of quality logic. Hence the introduction and implementations of Sharia as alternative legal code in Nigeria are major steps towards disintegration. This work in adopting socio-historical method of investigation, affirms that the secular state of Nigeria and its maintenance must be given supreme consideration in Nigerian agenda, if she must attain her desired nationhood.
The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts
Matthew R. Gingo, G. K. Balasubramani, Lawrence Kingsley, Charles R. Rinaldo, Christine B. Alden, Roger Detels, Ruth M. Greenblatt, Nancy A. Hessol, Susan Holman, Laurence Huang, Eric C. Kleerup, John Phair, Sarah H. Sutton, Eric C. Seaberg, Joseph B. Margolick, Stephen R. Wisniewski, Alison Morris
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058812
Abstract: Objective To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women’s Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001). Conclusion HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.
Ensemble Generation and the Influence of Protein Flexibility on Geometric Tunnel Prediction in Cytochrome P450 Enzymes
Laura J. Kingsley, Markus A. Lill
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099408
Abstract: Computational prediction of ligand entry and egress paths in proteins has become an emerging topic in computational biology and has proven useful in fields such as protein engineering and drug design. Geometric tunnel prediction programs, such as Caver3.0 and MolAxis, are computationally efficient methods to identify potential ligand entry and egress routes in proteins. Although many geometric tunnel programs are designed to accommodate a single input structure, the increasingly recognized importance of protein flexibility in tunnel formation and behavior has led to the more widespread use of protein ensembles in tunnel prediction. However, there has not yet been an attempt to directly investigate the influence of ensemble size and composition on geometric tunnel prediction. In this study, we compared tunnels found in a single crystal structure to ensembles of various sizes generated using different methods on both the apo and holo forms of cytochrome P450 enzymes CYP119, CYP2C9, and CYP3A4. Several protein structure clustering methods were tested in an attempt to generate smaller ensembles that were capable of reproducing the data from larger ensembles. Ultimately, we found that by including members from both the apo and holo data sets, we could produce ensembles containing less than 15 members that were comparable to apo or holo ensembles containing over 100 members. Furthermore, we found that, in the absence of either apo or holo crystal structure data, pseudo-apo or –holo ensembles (e.g. adding ligand to apo protein throughout MD simulations) could be used to resemble the structural ensembles of the corresponding apo and holo ensembles, respectively. Our findings not only further highlight the importance of including protein flexibility in geometric tunnel prediction, but also suggest that smaller ensembles can be as capable as larger ensembles at capturing many of the protein motions important for tunnel prediction at a lower computational cost.
Hebbian Crosstalk Prevents Nonlinear Unsupervised Learning
Kingsley J. A. Cox,Paul R. Adams
Quantitative Biology , 2008,
Abstract: Learning is thought to occur by localized, experience-induced changes in the strength of synaptic connections between neurons. Recent work has shown that activity-dependent changes at one connection can affect changes at others (crosstalk). We studied the role of such crosstalk in nonlinear Hebbian learning using a neural network implementation of Independent Components Analysis (ICA). We find that there is a sudden qualitative change in the performance of the network at a critical crosstalk level and discuss the implications of this for nonlinear learning from higher-order correlations in the neocortex.
Hocus-Socus: An Error Catastrophe for Complex Hebbian Learning Implies Neocortical Proofreading
Kingsley J. A. Cox,Paul R. Adams
Quantitative Biology , 2010,
Abstract: The neocortex is widely believed to be the seat of intelligence and "mind". However, it's unclear what "mind" is, or how the special features of neocortex enable it, though likely "connectionist" principles are involved *A. The key to intelligence1 is learning relationships between large numbers of signals (such as pixel values), rather than memorizing explicit patterns. Causes (such as objects) can then be inferred from a learned internal model. These relationships fall into 2 classes: simple pairwise or second-order correlations (socs), and complex, and vastly more numerous, higher-order correlations (hocsB), such as the product of 3 or more pixels averaged over a set of images. Thus if 3 pixels correlate, they may give an "edge". Neurons with "Hebbian" synapses (changing strength in response to input-output spike-coincidences) are sensitive to such correlations, and it's likely that learned internal models use such neurons. Because output firing depends on input firing via the relevant connection strengths, Hebbian learning provides, in a feedback manner, sensitivity to input correlations. Hocs are vital, since they express "interesting" structure2 (e.g. edges), but their detection requires nonlinear rules operating at synapses of individual neurons. Here we report that in single model neurons learning from hocs fails, and defaults to socs, if nonlinear Hebbian rules are not sufficiently connection-specific. Such failure would inevitably occur if a neuron's input synapses were too crowded, and would undermine biological connectionism. Since the cortex must be hoc-sensitive to achieve the type of learning enabling mind, we propose it uses known, detailed but poorly understood circuitry and physiology to "proofread" Hebbian connections. Analogous DNA proofreading allows evolution of complex genomes (i.e. "life").
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