7,505 research outputs found

    Marketing Research and Children’s Consumer Privacy Rights: A Battle in the Digital Age

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    Advancements in technology and social media have led to a decreased level of personal data privacy. Companies are now provided with limitless ways to extract information about their customers, even without their knowledge. This is especially concerning when it is the personal information of a child that is being collected, as in the United States, few regulations exist to protect them on social media. Even fewer regulations exist to protect children between the ages of thirteen and seventeen. The purpose of this Note is to discuss the importance between market research practices and children’s consumer privacy rights in the digital age. This Note discusses proposed solutions including adopting the United Nations Convention on the Rights of a Child to better protect children ages thirteen through seventeen, as well as reforming the current Children’s Online Privacy Protection Act, and criticism of parental control

    Tectonic implications of the Brawley earthquake swarm, Imperial Valley, California, January 1975

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    The Brawley earthquake swarm provided a unique opportunity for studying a highly interesting tectonic region. The swarm was most intense for a period of 4 days including 75 events with M_L between 3.0 and 4.7 with a spatial extent of 12 km. Precise relative hypocenters were obtained for 264 earthquakes (M_L ≧ 1.5) using a master event method to calibrate the USGS Imperial Valley array. These locations together with well-constrained focal mechanisms for 16 of the largest events suggest faulting on at least three distinct structures. Hypocentral depths ranged from 4 to 8 km, compared to a basement depth of about 6 km for this part of the Imperial Valley. The swarm began on a nearly vertical right-lateral fault striking N8°W (Brawley fault) about 8 km southeast of Brawley at a point which had experienced enhanced shallow seismicity during the preceding 4 days. The seismicity migrated bilaterally north and south from this point at a constant velocity of 0.5 km/hr terminating to the north on a steeply south dipping, N50°E-striking fault. This structure is on trend with splays associated with the northern end of ground breakage of the 1940 Imperial Valley earthquake. To the south the seismicity ended near the northern end of the 10 km of surface rupture mapped by R. V. Sharp, which continues on strike to a point near the Imperial fault. Tectonic interpretations include the transfer of right-lateral offset from the Imperial fault to the Brawley fault associated with the formation of a closed depression bounded on the west and east by these two faults

    Extremal Bounds on Earthquake Movement from Geodetic Data: Application to the Landers Earthquake

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    We present a technique to place quantifiable bounds on the moment of an earthquake from geodetic data, assuming known fault geometry. Application of this technique to the 1992 Landers earthquake shows that the moment must have been between 0.84 and 1.15 × 10^(20) Nm with 90% confidence (M 7.25 to 7.34). We also find that to satisfy the data to this same level of confidence, the slip on the fault must have exceeded 7 m in at least one location, in good agreement with field mapping of the surface rupture

    Quantification of dendritic and axonal growth after injury to the auditory system of the adult cricket Gryllus bimaculatus

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    Dendrite and axon growth and branching during development are regulated by a complex set of intracellular and external signals. However, the cues that maintain or influence adult neuronal morphology are less well understood. Injury and deafferentation tend to have negative effects on adult nervous systems. An interesting example of injury-induced compensatory growth is seen in the cricket, Gryllus bimaculatus. After unilateral loss of an ear in the adult cricket, auditory neurons within the central nervous system (CNS) sprout to compensate for the injury. Specifically, after being deafferented, ascending neurons (AN-1 and AN-2) send dendrites across the midline of the prothoracic ganglion where they receive input from auditory afferents that project through the contralateral auditory nerve (N5). Deafferentation also triggers contralateral N5 axonal growth. In this study, we quantified AN dendritic and N5 axonal growth at 30 h, as well as at 3, 5, 7, 14, and 20 days after deafferentation in adult crickets. Significant differences in the rates of dendritic growth between males and females were noted. In females, dendritic growth rates were non-linear; a rapid burst of dendritic extension in the first few days was followed by a plateau reached at 3 days after deafferentation. In males, however, dendritic growth rates were linear, with dendrites growing steadily over time and reaching lengths, on average, twice as long as in females. On the other hand, rates of N5 axonal growth showed no significant sexual dimorphism and were linear. Within each animal, the growth rates of dendrites and axons were not correlated, indicating that independent factors likely influence dendritic and axonal growth in response to injury in this system. Our findings provide a basis for future study of the cellular features that allow differing dendrite and axon growth patterns as well as sexually dimorphic dendritic growth in response to deafferentation

    Staged inertial microfluidic focusing for complex fluid enrichment

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    Microfluidic inertial focusing reliably and passively aligns small particles and cells through a combination of competing inertial fluid forces. The equilibrium behavior of inertially focused particles in straight channels has been extensively characterized and has been shown to be a strong function of channel size, geometry and particle size. We demonstrate that channels of varying geometry may be combined to produce a staged device capable of high throughput particle and cell concentration and efficient single pass complex fluid enrichment. Straight and asymmetrically curved microchannels were combined in series to accelerate focusing dynamics and improve concentration efficiency. We have investigated single and multiple pass concentration efficiency and results indicate that these devices are appropriate for routine cell handling operations, including buffer exchange. We demonstrate the utility of these devices by performing a ubiquitous fluorescence staining assay on-chip while sacrificing very little sample or processing time relative to centrifugation. Staged concentration is particularly desirable for point of care settings in which more conventional instrumentation is impractical or cost-prohibitive.United States. Department of Defense (Congressionally Directed Medical Research Program, Prostate Cancer Research Program Award number W81XWH-13-1-0272)University of Wyoming. IDeA Networks of Biomedical Research Excellence (program P20RR016474)University of Wyoming. IDeA Networks of Biomedical Research Excellence (program P20GM103432)United States. Department of Defense (Congressionally Directed Medical Research Program, Prostate Cancer Research Program Award number W81XWH-13-1-0273)United States. National Aeronautics and Space Administration (Wyoming NASA Space Grant Consortium (NASA Grant #NNX10A095H))National Science Foundation (U.S.) (Wyoming Experimental Program to Stimulate Competitive Research (Grant EPS-0447681)

    On the role of -vinylpyrrolidone in the aqueous radical-initiated copolymerization with PEGDA mediated by eosin Y in the presence of O[subscript 2]

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    The photochemistry of eosin Y has attracted attention for its role in visible-light induced polymerization reactions that proceed in the presence of ambient oxygen to form various macromolecular architectures that are useful for a wide range of applications, including biosensing and drug delivery. N-Vinylpyrrolidone (NVP) has been employed as a comonomer in the eosin-mediated synthesis of hydrogels with polyethylene glycol (PEG) based multifunctional monomers to aid in reducing oxygen inhibition and enhancing the rate of radical polymerization and the final conversion. However, the mechanism by which NVP reduces the oxygen inhibition time (t[subscript inh]) remains unclear. Additionally, no investigations were found on the integration of NVP into the radical-generating photocatalytic mechanism of eosin Y. Towards a better understanding of eosin-mediated synthesis of PEG-based hydrogels, we analyzed the effect of NVP on the steady-state kinetics of the aqueous NVP/PEG-diacrylate copolymerization reaction. In this case, the reduction in t[subscript inh] is lower than that reported for copolymerization with neat (meth)acrylate monomers. We propose the formation of a ground-state complex between eosin and NVP as the main reason for the reduction in oxygen inhibition and contrast it with previous theories. In addition, we discuss the role of this eosin/NVP complex and cross-propagation kinetics to explain the ∌70% increase in the initial rate of polymerization upon addition of NVP. The effect of cross-propagation kinetics is enhanced at the later stages, leading to a 10% increase in final vinyl conversion in this relatively mobile network. By analyzing the change in the scaling of the eosin decay coefficient as a function of light intensity during and after oxygen inhibition, we then link eosin inactivation to radical termination kinetics. Finally, we discuss the role of radical recombination between semireduced eosin and the propagating radicals as an additional eosin inactivation route by which leuco-eosin ends tethered to the network. These insights contribute to a thorough understanding of visible-light activated polymerization in the presence of oxygen and of the role of NVP in eosin-mediated radical production.Consejo Nacional de Ciencia y Tecnología (Mexico) (Award I0010-2015-01-263622/I0010-2016-02-275449)Kwanjeong Educational Foundation (Korea) (Scholarship)National Science Foundation (U.S.). Graduate Research Fellowship ProgramBurroughs Wellcome Fund (Career Award

    Maximum tumor diameter is associated with event-free survival in PET-negative patients with stage I/IIA Hodgkin lymphoma.

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    Introduction: the high cure rates achieved in early-stage (ES) Hodgkin lymphoma (HL) are one of the great successes of hemato-oncology, but late treatment-related toxicity undermines long-term survival. Improving overall survival and quality of life further will require maintaining disease control while potentially de-escalating chemotherapy and/or omitting radiotherapy to reduce late toxicity. Accurate stratification of patients is required to facilitate individualized treatment approaches. Response assessment using 18F-fluorodeoxyglucose positron emission tomography (PET) is a powerful predictor of outcome in HL,1,2 and has been used in multiple studies, including the United Kingdom National Cancer Research Institute Randomised Phase III Trial to Determine the Role of FDG–PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease (UK NCRI RAPID) trial, to investigate whether patients achieving complete metabolic remission (CMR) can be treated with chemotherapy alone.3-5 These PET-adapted trials have demonstrated that omitting radiotherapy results in higher relapse rates, but without compromising overall survival.3-5 For the 75% of patients who achieved CMR in RAPID, neither baseline clinical risk stratification (favorable/unfavorable) nor PET (Deauville score 1/2) predicted disease relapse; additional biomarkers are needed.1 Tumor bulk has long been recognized as prognostic in HL,1,6 but there remains uncertainty about the significance and definition of bulk in the era of PET-adapted treatment.7 We performed a subsidiary analysis of RAPID to assess the prognostic value of baseline maximum tumor dimension (MTD) in patients achieving CMR. Methods: ee have previously reported the RAPID trial design, primary results, and outcomes according to pretreatment risk stratification and PET score.1,3 Patients were aged 16 to 75 years with untreated ES-HL and without B-symptoms or mediastinal bulk (mass > 1/3 internal mediastinal diameter at T5/6).6 Metabolic response after 3 cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) was centrally assessed using PET (N = 562). Patients with CMR (ie, Deauville score 1-2) were randomly assigned to receive involved field radiotherapy (IFRT; n = 208) or no further therapy (NFT; n = 211). PET-positive patients (score, 3-5; n = 143) received a fourth cycle of ABVD and IFRT. Baseline disease assessment was performed by computed tomography, and bidimensional target lesion measurements were reported by local radiologists in millimeters. The association of baseline MTD with HL-related event-free survival (EFS: progression or HL-related death) and progression-free survival (PFS) (progression or any-cause death) was assessed using Kaplan-Meier and Cox regression analyses. Non-HL deaths were either related to primary treatment toxicity or occurred in HL remission.1 United Kingdom ethical approval for the RAPID trial was via the UK Multicentre Research ethics committee. Results and discussion: baseline patient characteristics have been previously described.1 Median age was 34 years (range, 16-75 years); 184 (37.4%) of 492 patients had unfavorable risk by European Organisation for Research and Treatment of Cancer criteria, and 155 (32.3%) of 480 by German Hodgkin Study Groupcriteria. Median MTD for patients achieving CMR was 3.0 cm (interquartile range, 2.0-4.0 cm) and 3.0 cm (interquartile range, 1.8-4.5 cm) in the NFT and IFRT groups, respectively, whereas PET-positive patients had a median MTD of 3.9 cm (interquartile range, 2.8-5.1 cm). After a median follow-up of 61.6 m, 44 HL progression events occurred: 21 NFT, 9 IFRT and 14 PET-positive. No patient received salvage treatment without documented progression. Only 5 HL-related deaths occurred (1 IFRT, 4 PET-positive), and 12 non-HL deaths (4 NFT, 6 IFRT, 2 PET-positive).1 For patients with CMR (N = 419), there was a strong association between MTD and EFS (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.02-1.39; P = .02), adjusting for treatment group, with an approximate 19% increase in HL risk per centimeter increase in MTD. The association was similar in both treatment groups (NFT HR, 1.20 [95% CI, 0.99-1.44; P = .06]; IFRT HR, 1.19 [95% CI, 0.92-1.55; P = .19]). The observed effect sizes did not markedly change after adjusting for baseline clinical risk factors, and similar results were observed for PFS (supplemental Table 1). In contrast, for PET-positive patients, there was no association between MTD and EFS (HR, 0.88; 95% CI, 0.70-1.11; P = .29) or PFS (HR, 0.87; 95% CI, 0.70-1.08; P = .21). In an exploratory analysis within the NFT group, MTD was dichotomized using increasing 1-cm intervals to investigate the relationship between MTD thresholds and EFS. The largest effect size was observed with an MTD threshold of ≄5 cm (Table 1). Similar results were observed for PFS; this threshold also performed best in time-dependent receiver operating characteristic curve analyses. It was not possible to assess MTD thresholds in the IFRT group with only 9 events. Among all randomized patients, 79 (18.9%) had MTD of ≄5 cm, the majority with mediastinal (n = 43), supraclavicular (n = 17), or cervical (n = 16) locations. Five-year EFS for patients with MTD of ≄5 cm randomly assigned to NFT and IFRT was 79.3% (n = 39; 95% CI, 66.6%-92.0%) and 94.9% (n = 40; 95% CI, 88.0%-100%), respectively (P = .03; Figure 1)

    In-depth characterization of the fluorescent signal of HyPer, a probe for hydrogen peroxide, in bacteria exposed to external oxidative stress

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    Genetically encoded, fluorescent biosensors have been developed to probe the activities of various signaling molecules inside cells ranging from changes in intracellular ion concentrations to dynamics of lipid second messengers. HyPer is a member of this class of biosensors and is the first to dynamically respond to hydrogen peroxide (H[subscript 2]O[subscript 2]), a reactive oxygen species that functions as a signaling molecule. However, detailed characterization of HyPer's signal is not currently available within the context of bacteria exposed to external oxidative stress, which occurs in the immunological response of higher organisms against invasive pathogenic bacteria. Here, we performed this characterization, specifically in Escherichia coli exposed to external H[subscript 2]O[subscript 2]. We found that the temporal behavior of the signal does not correspond exactly to peroxide concentration in the system as a function of time and expression of the sensor decreases the peroxide scavenging activity of the cell. We also determined the effects of cell number, both before and after normalization of externally added H[subscript 2]O[subscript 2] to the number of cells. Finally, we report quantitative characteristics of HyPer's signal in this context, including the dynamic range of the signal, the signal-to-noise ratio, and the half saturation constant. These parameters show statistically meaningful differences in signal between two commonly used strains of E. coli, demonstrating how signal can vary with strain. Taken together, our results establish a systematic, quantitative framework for researchers seeking to better understand the role of H[subscript 2]O[subscript 2] in the immunological response against bacteria, and for understanding potential differences in the details of HyPer's quantitative performance across studies.Massachusetts Institute of Technology. James H. Ferry Fund for Innovation in Research EducationNational Science Foundation (U.S.) (NSF Graduate Research Fellowship)Massachusetts Institute of Technology (Joseph R. Mares endowed chair in chemical engineering)Burroughs Wellcome Fund (Career Award at the Scientific Interface

    The Importance of Reporting Housing and Husbandry in Rat Research

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    In 1963, the National Institutes of Health (NIH) first issued guidelines for animal housing and husbandry. The most recent 2010 revision emphasizes animal care “in ways judged to be scientifically, technically, and humanely appropriate” (National Institutes of Health, 2010, p. XIII). The goal of these guidelines is to ensure humanitarian treatment of animals and to optimize the quality of research. Although these animal care guidelines cover a substantial amount of information regarding animal housing and husbandry, researchers generally do not report all these variables (see Table ​Table1).1). The importance of housing and husbandry conditions with respect to standardization across different research laboratories has been debated previously (Crabbe et al., 1999; Van Der Staay and Steckler, 2002; Wahlsten et al., 2003; Wolfer et al., 2004; Van Der Staay, 2006; Richter et al., 2010, 2011). This paper focuses on several animal husbandry and housing issues that are particularly relevant to stress responses in rats, including transportation, handling, cage changing, housing conditions, light levels and the light–dark cycle. We argue that these key animal housing and husbandry variables should be reported in greater detail in an effort to raise awareness about extraneous experimental variables, especially those that have the potential to interact with the stress response

    Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe

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    Redox cancer therapeutics target the increased reliance on intracellular antioxidant systems and enhanced susceptibility to oxidant-induced stress of some cancer cells compared to normal cells. Many of these therapeutics are thought to perturb intracellular levels of the oxidant hydrogen peroxide (H[subscript 2]O[subscript 2]), a signaling molecule that modulates a number of different processes in human cells. However, fluorescent probes for this species remain limited in their ability to detect the small perturbations induced during successful treatments. We report a fluorescent sensor based upon human peroxiredoxin-2, which acts as the natural indicator of small H[subscript 2]O[subscript 2] fluctuations in human cells. The new probe reveals peroxide-induced oxidation in human cells below the detection limit of current probes, as well as peroxiredoxin-2 oxidation caused by two different redox cancer therapeutics in living cells. This capability will be useful in elucidating the mechanism of current redox-based therapeutics and in developing new ones.National Science Foundation (U.S.). Graduate Research Fellowship ProgramSamsung FellowshipMassachusetts Institute of Technology (Haas Family Fellowship in Chemical Engineering
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