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Search Results: 1 - 10 of 299521 matches for " Barry J Goldstein "
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Use of an Anaerobic Chamber Environment for the Assay of Endogenous Cellular Protein-Tyrosine Phosphatase Activities
Zhu Li,Goldstein Barry
Biological Procedures Online , 2002, DOI: 10.1251/bpo28
Abstract: Protein-tyrosine phosphatases (PTPases) have a catalytic cysteine residue whose reduced state is integral to the reaction mechanism. Since exposure to air can artifactually oxidize this highly reactive thiol, PTPase assays have typically used potent reducing agents to reactivate the enzymes present; however, this approach does not allow for the measurement of the endogenous PTPase activity directly isolated from the in vivo cellular environment. Here we provide a method for using an anaerobic chamber to preserve the activity of the total PTPase complement in a tissue lysate or of an immunoprecipitated PTPase homolog to characterize their endogenous activation state. Comparison with a sample treated with biochemical reducing agents allows the determination of the activatable (reducible) fraction of the endogenous PTPase pool.
Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis
Samuel S Engel, Gregory T Golm, Deborah Shapiro, Michael J Davies, Keith D Kaufman, Barry J Goldstein
Cardiovascular Diabetology , 2013, DOI: 10.1186/1475-2840-12-3
Abstract: A post hoc assessment of cardiovascular safety in 14,611 patients was performed by pooling data from 25 double-blind studies, which randomised patients at baseline to sitagliptin 100 mg/day or a non-sitagliptin comparator (i.e., non-exposed). Included studies were limited to those at least 12 weeks in duration (range: 12 to 104 weeks). Patient-level data were used in this analysis of major adverse cardiovascular events (MACE) including ischaemic events and cardiovascular deaths. Analyses were performed in three cohorts: the entire 25-study cohort, the cohort from placebo-controlled portions of studies (n=19), and the cohort from studies comparing sitagliptin to a sulphonylurea (n=3).In the entire cohort analysis, 78 patients had at least 1 reported MACE-related event, with 40 in the sitagliptin group and 38 in the non-exposed group. The exposure-adjusted incidence rate was 0.65 per 100 patient-years in the sitagliptin group and 0.74 in the non-exposed group (incidence rate ratio = 0.83 [95% confidence interval (CI): 0.53, 1.30]). In the analysis comparing sitagliptin to placebo, the exposure-adjusted incidence rate was 0.80 per 100-patient-years with sitagliptin and 0.76 with placebo (incidence rate ratio = 1.01 [95% CI: 0.55, 1.86]). In the analysis comparing sitagliptin to sulphonylurea, the exposure-adjusted incidence rate was 0.00 per 100 patient-years with sitagliptin and 0.86 with sulphonylurea (incidence rate ratio = 0.00 [95% CI: 0.00, 0.31]).A pooled analysis of 25 randomised clinical trials does not indicate that treatment with sitagliptin increases cardiovascular risk in patients with type 2 diabetes mellitus. In a subanalysis, a higher rate of cardiovascular-related events was associated with sulphonylurea relative to sitagliptin.
Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes
Debora Williams-Herman, Samuel S Engel, Elizabeth Round, Jeremy Johnson, Gregory T Golm, Hua Guo, Bret J Musser, Michael J Davies, Keith D Kaufman, Barry J Goldstein
BMC Endocrine Disorders , 2010, DOI: 10.1186/1472-6823-10-7
Abstract: The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day (N = 5,429; sitagliptin group) or a comparator agent (placebo or an active comparator) (N = 4,817; non-exposed group). The 19 studies from which this pooled population was drawn represent the double-blind, randomized studies that included patients treated with the usual clinical dose of sitagliptin (100 mg/day) for between 12 weeks and 2 years and for which results were available as of July 2009. These 19 studies assessed sitagliptin taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin). Patients in the non-exposed group were taking placebo, metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin. The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events.Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups, except for an increased incidence of drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were also generally similar between the two groups, except for increased incidence rates of hypoglycemia, related to the greater use of a sulfonylurea, and diarrhea, related to the greater use of metformin, in the non-exposed group and constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events.In this updated pooled safety analysis of data from 10,246 patients with type 2 diabetes, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration.The safety and tolerability of sitagliptin, a dipeptidyl peptidase-4 (
Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury
Katharine Eakin, Renana Baratz-Goldstein, Chiam G. Pick, Ofra Zindel, Carey D. Balaban, Michael E. Hoffer, Megan Lockwood, Jonathan Miller, Barry J. Hoffer
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090617
Abstract: In this study, using two different injury models in two different species, we found that early post-injury treatment with N-Acetyl Cysteine (NAC) reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting [1], to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI). For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30–60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man.
Optimization of a Novel Non-invasive Oral Sampling Technique for Zoonotic Pathogen Surveillance in Nonhuman Primates
Tierra Smiley Evans?,Peter A. Barry,Kirsten V. Gilardi?,Tracey Goldstein,Jesse D. Deere?,Joseph Fike?,JoAnn Yee?,Benard J Ssebide?,Dibesh Karmacharya?,Michael R. Cranfield
PLOS Neglected Tropical Diseases , 2015, DOI: 10.1371/journal.pntd.0003813
Abstract: Free-ranging nonhuman primates are frequent sources of zoonotic pathogens due to their physiologic similarity and in many tropical regions, close contact with humans. Many high-risk disease transmission interfaces have not been monitored for zoonotic pathogens due to difficulties inherent to invasive sampling of free-ranging wildlife. Non-invasive surveillance of nonhuman primates for pathogens with high potential for spillover into humans is therefore critical for understanding disease ecology of existing zoonotic pathogen burdens and identifying communities where zoonotic diseases are likely to emerge in the future. We developed a non-invasive oral sampling technique using ropes distributed to nonhuman primates to target viruses shed in the oral cavity, which through bite wounds and discarded food, could be transmitted to people. Optimization was performed by testing paired rope and oral swabs from laboratory colony rhesus macaques for rhesus cytomegalovirus (RhCMV) and simian foamy virus (SFV) and implementing the technique with free-ranging terrestrial and arboreal nonhuman primate species in Uganda and Nepal. Both ubiquitous DNA and RNA viruses, RhCMV and SFV, were detected in oral samples collected from ropes distributed to laboratory colony macaques and SFV was detected in free-ranging macaques and olive baboons. Our study describes a technique that can be used for disease surveillance in free-ranging nonhuman primates and, potentially, other wildlife species when invasive sampling techniques may not be feasible.
Kubo formulas for viscosity: Hall viscosity, Ward identities, and the relation with conductivity
Barry Bradlyn,Moshe Goldstein,N. Read
Physics , 2012, DOI: 10.1103/PhysRevB.86.245309
Abstract: We derive from first principles the Kubo formulas for the stress-stress response function at zero wavevector that can be used to define the full complex frequency-dependent viscosity tensor, both with and without a uniform magnetic field. The formulas in the existing literature are frequently incomplete, incorrect, or lack a derivation; in particular, Hall viscosity is overlooked. Our approach begins from the response to a uniform external strain field, which is an active time-dependent coordinate transformation in d space dimensions. These transformations form the group GL(d,R) of invertible matrices, and the infinitesimal generators are called strain generators. These enable us to express the Kubo formula in different ways, related by Ward identities; some of these make contact with the adiabatic transport approach. For Galilean-invariant systems, we derive a relation between the stress response tensor and the conductivity tensor that is valid at all frequencies and in both the presence and absence of a magnetic field. In the presence of a magnetic field and at low frequency, this yields a relation between the Hall viscosity, the q^2 part of the Hall conductivity, the inverse compressibility (suitably defined), and the diverging part of the shear viscosity (if any); this relation generalizes a result found recently. We show that the correct value of the Hall viscosity at zero frequency can be obtained (at least in the absence of low-frequency bulk and shear viscosity) by assuming that there is an orbital spin per particle that couples to a perturbing electromagnetic field as a magnetization per particle. We study several examples as checks on our formulation.
Early 20th Century Climate-Driven Shift in the Dynamics of Forest Tent Caterpillar Outbreaks  [PDF]
Barry J. Cooke, Jens Roland
American Journal of Climate Change (AJCC) , 2018, DOI: 10.4236/ajcc.2018.72017
Abstract: Using tree-ring analysis, we show that the dynamics of forest tent caterpillar [Malacosoma disstria (Hbn.)] outbreaks in Alberta, Canada shifted at the turn of the 20th century from cyclic, synchronous behaviour 1850-1910 to complex, asynchronous behavior 1910-1993. This shift in dynamics coincided with the emergence in 1910 of a latitudinal gradient in outbreak stability and periodicity reflecting a similar gradient in the periodicity of winter temperatures. We postulate that the synchronizing strength of winter temperatures has diminished as a result of climate warming, and that any synchronizing strength due to inter-population migration has been superseded by regionalized patterns of periodic forcing caused by weak low-frequency variability in winter temperatures. We speculate that a decrease in polar vorticity at the start of the 20th century led to increased meridional jet stream flow and more frequent arctic weather anomalies, resulting in a loss of synchronous decadal periodicity in outbreak occurrence. These changes in insect disturbance probabilities, including rising uncertainty, have profound consequences for forest disturbance risk management.
Nonsingular Efficient Modeling of Rotations in 3-space using three components
Norman J. Goldstein
Computer Science , 2010,
Abstract: This article introduces yet another representation of rotations in 3-space. The rotations form a 3-dimensional projective space, which fact has not been exploited in Computer Science. We use the four affine patches of this projective space to parametrize the rotations. This affine patch representation is more compact than quaternions (which require 4 components for calculations), encompasses the entire rotation group without singularities (unlike the Euler angles and rotation vector approaches), and requires only ratios of linear or quadratic polynomials for basic computations (unlike the Euler angles and rotation vector approaches which require transcendental functions). As an example, we derive the differential equation for the integration of angular velocity using this affine patch representation of rotations. We remark that the complexity of this equation is the same as the corresponding quaternion equation, but has advantages over the quaternion approach e.g. renormalization to unit length is not required, and state space has no dead directions.
Sanitary Hazards and Microbial Quality of Open Dug Wells in the Maldives Islands  [PDF]
Shivasorupy Barthiban, Barry J. Lloyd, Mathias Maier
Journal of Water Resource and Protection (JWARP) , 2012, DOI: 10.4236/jwarp.2012.47055
Abstract: Concern for saline and microbial quality post-December 2004 tsunami, led to a field based surveillance study to systematically investigate the sanitary hazards which cause faecal contamination of groundwater. In seven islands, two duplicate sample sets, in two surveys, revealed that only 6.4% of the 173 well water samples (combining both surveys) satisfied the WHO Drinking Water Quality Guideline for 44°C thermo-tolerant (Faecal) Coliform (FC) indicator value (zero cfu/100 ml sample). Based on a combined risk analysis of Sanitary Hazard Score (SHS) and FC counts, more than 57.7% of the study wells were classified as at very high (FC: 100 to >1,000 cfu/100ml; and SHS: ≥ 9) microbial health risk. During this study, fundamental changes were made to the published generic sanitary inspection method (WHO, 1997) for identifying sanitary hazards, for its application in the extremely vulnerable hydro-geological setting of the Maldives. However, the most important hazard controlling the intensity of faecal contamination in the Maldives is the safe separation distance between a latrine seepage point and the well. It was demonstrated that, due to the prevailing hydro-geological conditions and the well and sanitation system densities, safe separation distance cannot be achieved. Consequently, septic tank effluent quality must be greatly improved.
Splenomegaly, hypersplenism, and hereditary disorders with splenomegaly  [PDF]
Neal J. Weinreb, Barry E. Rosenbloom
Open Journal of Genetics (OJGen) , 2013, DOI: 10.4236/ojgen.2013.31004
Abstract:
Splenomegaly, sometimes of massive extent, occurs in a large number of hereditary diseases, some relatively prevalent and others, rare to ultra-rare. Because physicians are often unfamiliar with the less common disorders, patients may suffer because of diagnostic delay or diagnostic error and may undergo invasive, non-innocuous procedures such as splenectomy that are potentially avoidable were the correct diagnosis suspected. In this review article, we discuss the definition and clinical ramifications of “massive” splenomegaly and describe several rare genetic disorders that are sometimes associated with marked splenic enlargement as well as four additional hereditary “splenomegalic” lysosomal storage diseases (cholesterol esterase storage disease, Niemann-Pick C disease, acid sphingomyelinase deficiency disease, Gaucher disease) in which approved or promising experimental treatments should generally obviate the need for palliative splenectomy. We also summarize current concepts about the appropriate use of splenectomy in patients with β-thalassemia, hereditary spherocytosis and Gaucher disease and discuss surgical alternatives to classical total splenectomy for these disorders.
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