1,200 research outputs found
Temptation: A Biblical and Psychological Approach
Reviewed Book: Oates, Wayne Edward. Temptation: A Biblical and Psychological Approach. Louisville, Ky: Westminster/John Knox Press, 1991
A Neural Network Model for the Development of Simple and Complex Cell Receptive Fields Within Cortical Maps of Orientation and Ocular Dominance
Prenatal development of the primary visual cortex leads to simple cells with spatially distinct and oriented ON and OFF subregions. These simple cells are organized into spatial maps of orientation and ocular dominance that exhibit singularities, fractures, and linear zones. On a finer spatial scale, simple cells occur that are sensitive to similar orientations but opposite contrast polarities, and exhibit both even-symmetric and odd-symmetric receptive fields. Pooling of outputs from oppositely polarized simple cells leads to complex cells that respond to both contrast polarities. A neural network model is described which simulates how simple and complex cells self-organize starting from unsegregated and unoriented geniculocortical inputs during prenatal development. Neighboring simple cells that are sensitive to opposite contrast polarities develop from a combination of spatially short-range inhibition and high-gain recurrent habituative excitation between cells that obey membrane equations. Habituation, or depression, of synapses controls reset of cell activations both through enhanced ON responses and OFF antagonistic rebounds. Orientation and ocular dominance maps form when high-gain medium-range recurrent excitation and long-range inhibition interact with the short-range mechanisms. The resulting structure clarifies how simple and complex cells contribute to perceptual processes such as texture segregation and perceptual grouping.Air Force Office of Scientific Research (F49620-92-J-0334); British Petroleum (BP 89A-1204); National Science Foundation (IRI-90-24877); Office of Naval Research (N00014-91-J-4100); Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409
Imaging FlowCytobot modified for high throughput by in-line acoustic focusing of sample particles
© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Limnology and Oceanography: Methods 15 (2017): 867–874, doi:10.1002/lom3.10205.Imaging FlowCytobot, a submersible instrument that measures optical properties and captures images of nano- and microplankton-sized particles, has proved useful in plankton studies, but its sampling rate is limited by the ability of hydrodynamic focusing to accurately position flowing sample particles. We show that IFCB's sampling rate can be increased at least several-fold by implementing in-line acoustic focusing upstream of the flow cell. Particles are forced to the center of flow by acoustic standing waves created by a piezo-electric transducer bonded to the sample capillary and driven at the appropriate frequency. With the particles of interest confined to the center of the sample flow, the increased size of the sample core that accompanies increased sample flow rate no longer degrades image and signal quality as it otherwise would. Temperature affects the optimum frequency (through its effect on the speed of sound in water), so a relationship between sample temperature and optimum frequency for acoustic focusing was determined and utilized to control the transducer. The modified instrument's performance was evaluated through analyses of artificial particles, phytoplankton cultures, and natural seawater samples and through deployments in coastal waters. The results show that large cells, especially dinoflagellates, are acoustically focused extremely effectively (which could enable, for example, > 10-fold increased sampling rate of harmful algal bloom species, if smaller cells are ignored), while for nearly all cell types typically monitored by IFCB, threefold faster data accumulation was achieved without any compromises. Further increases are possible with more sophisticated software and/or a faster camera.NSF Grant Numbers: OCE-1130140 , OCE-113113
Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of chemotherapeutic management and antiangiogenic treatment of newly diagnosed glioblastoma in adults
QUESTION: What is the role of temozolomide in the management of adult patients (aged 65 and under) with newly diagnosed glioblastoma?
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level I: Concurrent and post-irradiation Temozolomide (TMZ) in combination with radiotherapy and post-radiotherapy as described by Stupp et al. is recommended to improve both PFS and OS in adult patients with newly diagnosed GBM. There is no evidence that alterations in the dosing regimen have additional beneficial effect.
QUESTION: Is there benefit to adjuvant temozolomide treatment in elderly patients (\u3e 65 years old?).
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level III: Adjuvant TMZ treatment is suggested as a treatment option to improve PFS and OS in adult patients (over 70 years of age) with newly diagnosed GBM.
QUESTION: What is the role of local regional chemotherapy with BCNU biodegradable polymeric wafers in adult patients with newly diagnosed glioblastoma?
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level III: There is insufficient evidence for the use of BCNU wafers following resection in patients with newly diagnosed glioblastoma who undergo the Stupp protocol after surgery. Further studies of higher quality are suggested to understand the role of BCNU wafer and other locoregional therapy in the setting of Stupp Protocol.
QUESTION: What is the role of bevacizumab in the adult patient with newly diagnosed glioblastoma?
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level I: Bevacizumab in general is not recommended in the initial treatment of adult patients with newly diagnosed GBM. It continues to be strongly recommended that patients with newly diagnosed GBM be enrolled in properly designed clinical trials to assess the benefit of novel chemotherapeutic agents compared to standard therapy
Metabolism of profenofos to 4-bromo-2-chlorophenol, a specific and sensitive exposure biomarker.
Profenofos is a direct acting phosphorothioate organophosphorus (OP) pesticide capable of inhibiting β-esterases such as acetylcholinesterase, butyrylcholinesterase, and carboxylesterase. Profenofos is known to be detoxified to the biologically inactive metabolite, 4-bromo-2-chlorophenol (BCP); however, limited data are available regarding the use of urinary BCP as an exposure biomarker in humans. A pilot study conducted in Egyptian agriculture workers, demonstrated that urinary BCP levels prior to application (3.3-30.0 μg/g creatinine) were elevated to 34.5-3,566 μg/g creatinine during the time workers were applying profenofos to cotton fields. Subsequently, the in vitro enzymatic formation of BCP was examined using pooled human liver microsomes and recombinant human cytochrome P-450s (CYPs) incubated with profenofos. Of the nine human CYPs studied, only CYPs 3A4, 2B6, and 2C19 were able to metabolize profenofos to BCP. Kinetic studies indicated that CYP 2C19 has the lowest Km, 0.516 μM followed by 2B6 (Km=1.02 μM) and 3A4 (Km=18.9μM). The Vmax for BCP formation was 47.9, 25.1, and 19.2 nmol/min/nmol CYP for CYP2B6, 2C19, and 3A4, respectively. Intrinsic clearance (Vmax/Km) values of 48.8, 46.9, and 1.02 ml/min/nmol CYP 2C19, 2B6, and 3A4, respectively, indicate that CYP2C19 and CYP2B6 are primarily responsible for the detoxification of profenofos. These findings support the use of urinary BCP as a biomarker of exposure to profenofos in humans and suggest polymorphisms in CYP 2C19 and CYP 2B6 as potential biomarkers of susceptibility
Leelanau County Inland Lakes Project
Master of ScienceLandscape ArchitectureUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/114606/2/39015043175614.pd
Distributions of Pigments and Primary Production in a Gulf-Stream Meander
An investigation was made of physical effects of Gulf Stream meandering on the vertical and horizontal distributions of photosynthetic pigments and primary production. Cruises were conducted in the vicinity of a meander east of 73-degrees-W and north of 37-degrees-N from September 21 to October 5 (leg 1) and October 12-21, 1988 (leg 2), on the R/V Cape Hatteras. Relationships of photosynthesis (normalized to chlorophyll) to irradiance (P-1) did not show large horizontal variation, and water column composite P-I curves from leg 1 and leg 2 were similar. Therefore a single P-I curve derived from pooled data was used to model distributions of primary production. Distributions of photosynthetic pigments were characterized on the basis of in vivo fluorescence profiles and empirical relationships with extracted pigment concentrations. Subsurface irradiance was described using a spectral irradiance model. Cross sections of the Gulf Stream revealed consistently higher pigment concentrations and primary production on the slope water side. Along-stream variations in pigment distributions and primary production were apparently related to density structure influenced by meander circulation. Such variations were less pronounced during leg 2. which came after a transition from a well-defined meander interacting with a warm-core ring (leg 1) to a more linear stream (leg 2). Higher water-column-integrated primary production during leg 2 was attributed to mixing-induced nutrient injection and redistribution of chlorophyll in the photic zone
Capacitive Sensing of Intercalated H2O Molecules Using Graphene
Understanding the interactions of ambient molecules with graphene and
adjacent dielectrics is of fundamental importance for a range of graphene-based
devices, particularly sensors, where such interactions could influence the
operation of the device. It is well-known that water can be trapped underneath
graphene and its host substrate, however, the electrical effect of water
beneath graphene and the dynamics of how it changes with different ambient
conditions has not been quantified. Here, using a metal-oxide-graphene
variable-capacitor (varactor) structure, we show that graphene can be used to
capacitively sense the intercalation of water between graphene and HfO2 and
that this process is reversible on a fast time scale. Atomic force microscopy
is used to confirm the intercalation and quantify the displacement of graphene
as a function of humidity. Density functional theory simulations are used to
quantify the displacement of graphene induced by intercalated water and also
explain the observed Dirac point shifts as being due to the combined effect of
water and oxygen on the carrier concentration in the graphene. Finally,
molecular dynamics simulations indicate that a likely mechanism for the
intercalation involves adsorption and lateral diffusion of water molecules
beneath the graphene.Comment: E.J.O. and R.M. made an equal contribution to this wor
Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance
The identification of key tumorigenic events in Sonic Hedgehog (SHH) subgroup medulloblastomas (MBSHH) will be essential for the development of individualized therapies and improved outcomes. However, beyond confirmation of characteristic SHH pathway mutations, recent genome-wide sequencing studies have not revealed commonly mutated genes with widespread relevance as potential therapeutic targets. We therefore examined any role for epigenetic DNA methylation events in MBSHH using a cross-species approach to candidate identification, prioritization and validation. MBSHH-associated DNA methylation events were first identified in 216 subgrouped human medulloblastomas (50 MBSHH, 28 Wnt/Wingless, 44 Group 3 and 94 Group 4) and their conservation then assessed in tumors arising from four independent murine models of Shh medulloblastoma, alongside any role in tumorigenesis using functional assessments in mouse and human models. This strategy identified widespread regional CpG hypo-methylation of VAV1, leading to its elevated expression, as a conserved aberrant epigenetic event, which characterizes the majority of MBSHH tumors in both species, and is associated with a poor outcome in MBSHH patients. Moreover, direct modulation of VAV1 in mouse and human models revealed a critical role in tumor maintenance, and its abrogation markedly reduced medulloblastoma growth. Further, Vav1 activity regulated granule neuron precursor germinal zone exit and migration initiation in an ex vivo model of early postnatal cerebellar development. These findings establish VAV1 as a critical epigenetically regulated oncogene with a key role in MBSHH maintenance, and highlight its potential as a validated therapeutic target and prognostic biomarker for the improved therapy of medulloblastoma
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