2,008 research outputs found
'Follow me': a web-based, location-sharing architecture for large, indoor environments
We leverage the ubiquity of bluetooth-enabled devices and propose a decentralized, web-based architecture that allows users to share their location by following each other in the style of Twitter. We demonstrate a prototype that operates in a large building which generates a dataset of detected bluetooth devices at a rate of ~30 new devices per day, including the respective location where they were last detected. Users then query the dataset using their unique bluetooth ID and share their current location with their followers by means of unique URIs that they control. Our separation between producers (the building) and consumers (the users) of bluetooth device location data allows us to create socially-aware applications that respect user's privacy while limiting the software necessary to run on mobile devices to just a web browser
Construction of Non-Perturbative, Unitary Particle-Antiparticle Amplitudes for Finite Particle Number Scattering Formalisms
Starting from a unitary, Lorentz invariant two-particle scattering amplitude
, we show how to use an identification and replacement process to construct a
unique, unitary particle-antiparticle amplitude. This process differs from
conventional on-shell Mandelstam s,t,u crossing in that the input and
constructed amplitudes can be off-diagonal and off-energy shell. Further,
amplitudes are constructed using the invariant parameters which are appropriate
to use as driving terms in the multi-particle, multichannel non-perturbative,
cluster decomposable, relativistic scattering equations of the Faddeev-type
integral equations recently presented by Alfred, Kwizera, Lindesay and Noyes.
It is therefore anticipated that when so employed, the resulting multi-channel
solutions will also be unitary. The process preserves the usual
particle-antiparticle symmetries. To illustrate this process, we construct a
J=0 scattering length model chosen for simplicity. We also exhibit a class of
physical models which contain a finite quantum mass parameter and are Lorentz
invariant. These are constructed to reduce in the appropriate limits, and with
the proper choice of value and sign of the interaction parameter, to the
asymptotic solution of the non-relativistic Coulomb problem, including the
forward scattering singularity, the essential singularity in the phase, and the
Bohr bound-state spectrum
Calculation of the effect of random superfluid density on the temperature dependence of the penetration depth
Microscopic variations in composition or structure can lead to nanoscale
inhomogeneity in superconducting properties such as the magnetic penetration
depth, but measurements of these properties are usually made on longer length
scales. We solve a generalized London equation with a non-uniform penetration
depth, lambda(r), obtaining an approximate solution for the disorder-averaged
Meissner effect. We find that the effective penetration depth is different from
the average penetration depth and is sensitive to the details of the disorder.
These results indicate the need for caution when interpreting measurements of
the penetration depth and its temperature dependence in systems which may be
inhomogeneous
Control of inflorescence architecture in tomato by BTB/POZ transcriptional regulators
Plant productivity depends on inflorescences, flower-bearing shoots that originate from the stem cell populations of shoot meristems. Inflorescence architecture determines flower production, which can vary dramatically both between and within species. In tomato plants, formation of multiflowered inflorescences depends on a precisely timed process of meristem maturation mediated by the transcription factor gene TERMINATING FLOWER (TMF), but the underlying mechanism is unknown. We show that TMF protein acts together with homologs of the Arabidopsis BLADE-ON-PETIOLE (BOP) transcriptional cofactors, defined by the conserved BTB (Broad complex, Tramtrack, and Bric-a-brac)/POZ (POX virus and zinc finger) domain. TMF and three tomato BOPs (SlBOPs) interact with themselves and each other, and TMF recruits SlBOPs to the nucleus, suggesting formation of a transcriptional complex. Like TMF, SlBOP gene expression is highest during vegetative and transitional stages of meristem maturation, and CRISPR/Cas9 elimination of SlBOP function causes pleiotropic defects, most notably simplification of inflorescences into single flowers, resembling tmf mutants. Flowering defects are enhanced in higher-order slbop tmf mutants, suggesting that SlBOPs function with additional factors. In support of this, SlBOPs interact with TMF homologs, mutations in which cause phenotypes like slbop mutants. Our findings reveal a new flowering module defined by SlBOP-TMF family interactions that ensures a progressive meristem maturation to promote inflorescence complexity
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Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients With Colorectal Cancers: Correlation With Tissue Sequencing, Therapeutic Response, and Survival.
PurposeGenomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with colorectal cancers were correlated with clinical outcomes.Patients and methodsNext-generation sequencing of ctDNA (54- to 73-gene panel) was performed in 94 patients with colorectal cancer.ResultsMost patients (96%) had metastatic or recurrent disease at the time of blood draw. The median number of nonsynonymous alterations per patient was three (range, zero to 30). The most frequently aberrant genes were TP53 (52.1% of patients), KRAS (34%), and APC (28.7%). Concordance between tissue and blood next-generation sequencing ranged from 63.2% (APC) to 85.5% (BRAF). Altogether, 74 patients (79%) had one or more nonsynonymous alterations, 69 (73%) had one or more potentially actionable alterations, and 61 (65%) had an alteration actionable by a drug approved by the US Food and Drug Administration (on or off label). Lung metastases correlated with improved survival from diagnosis in univariable analysis. ctDNA of 5% or more from blood tests as well as EGFR and ERBB2 (HER2) nonsynonymous alterations correlated with worse survival (but only ERBB2 remained significant in multivariable analysis). No two patients had identical molecular portfolios. Overall, 65% versus 31% of patients treated with matched (n = 17) versus unmatched therapy (n = 18) after ctDNA testing achieved stable disease for 6 months or more, partial response, or complete response (P = .045); progression-free survival, 6.1 versus 2.3 months (P = .08); and survival not reached versus 9.4 months (P = .146; all by multivariable analysis).ConclusionPatients with colorectal cancer have heterogeneous ctDNA profiles, and most harbor potentially actionable ctDNA alterations. Matched therapy yielded higher rates of stable disease for 6 months or more, partial response, or complete response. ctDNA assessment may have clinical utility and merits further investigation
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Revisiting Epidermal Growth Factor Receptor (EGFR) Amplification as a Target for Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor DNA in Patients With Advanced Malignancies.
PurposeTo date, evidence for tissue epidermal growth factor receptor (EGFR) overexpression as a biomarker for anti-EGFR therapies has been weak. We investigated the genomic landscape of EGFR amplification in blood-derived cell-free tumor DNA (cfDNA) across diverse cancers and the role of anti-EGFR therapies in achieving response.MethodsWe assessed EGFR amplification status among 28,584 patients with malignancies evaluated by clinical-grade next-generation sequencing (NGS) of blood-derived cfDNA (54- to 73-gene panel). Furthermore, we curated the clinical characteristics of 1,434 patients at the University of California San Diego who had cfDNA testing by this NGS test.ResultsOverall, EGFR amplification was detected in cfDNA from 8.5% of patients (2,423 of 28,584), most commonly in colorectal (16.3% [458 of 2,807]), non-small-cell lung (9.0% [1,096 of 12,197]), and genitourinary cancers (8.1% [170 of 2,104]). Most patients had genomic coalterations (96.9% [95 of 98]), frequently involving genes affecting other tyrosine kinases (72.4% [71 of 98]), mitogen-activated protein kinase cascades (56.1% [55 of 98]), cell-cycle-associated signals (52.0% [51 of 98]), and the phosphoinositide 3-kinase pathway (35.7% [35 of 98]). EGFR amplification emerged in serial cfDNA after various anticancer therapies (n = 6), including checkpoint inhibitors (n = 4), suggesting a possible role for these amplifications in acquired resistance. Nine evaluable patients with EGFR amplification were treated with anti-EGFR-based regimens; five (55.6%) achieved partial responses, including three patients whose tissue NGS lacked EGFR amplification.ConclusionEGFR amplification was detected in cfDNA among 8.5% of 28,584 diverse cancers. Most patients had coexisting alterations. Responses were observed in five of nine patients who received EGFR inhibitors. Incorporating EGFR inhibitors into the treatment regimens of patients harboring EGFR amplification in cfDNA merits additional study
976-14 Immediate Heart Rate Response to Orthostatic Stress During β-blocker Therapy for Vasodepressor Syncope
Although β-blockers are preferred agents for therapy of vasodepressor syncope (VDS), they are not uniformly effective and their mechanism of action is incompletely understood. Since we have previously shown a differential therapeutic response to β-blocker therapy between pts with isoproterenol-independent [iso(-)] and isoproterenol-dependent [iso(+)] VDS during tilt table testing we sought to determine whether this was due to a differential heart rate (HR) response to orthostasis during β-blockade. We therefore examined immediate HR and blood pressure responses to upright tilt before and after initiation of therapy with atenolol (12.5–50mg daily) in 62 pts with VDS and positive tilt tests. The protocol comprised upright tilt (60°) for up to 60min followed by repeat tilt for 15min during isoproterenol (iso) infusion. Supine HR, mean arterial pressure (MAP) and pulse pressure (PP) were determined as the mean of 3 consecutive 1-min samples during supine rest; orthostatic HR, MAP, and PP were the mean of the samples recorded in the first 3min after upright tilt (before infusion of iso). Response to atenolol required completion of tilt with and without infusion of iso. There were 15 iso(-) pts and 47 iso(+) pts. The groups did not differ significantly in blood pressure response (MAP, PP) to orthostasis. Supine HR fell and the ΔHR in response to orthostasis was blunted during therapy in both groups:Baseline (Mean ± SD)Rx (Mean ± SD)Iso(+)Iso(-)pIso(+)Iso(-)pSupine HR69±1368±9NS57±958±8NSOrthostatic ΔHR8±712±9NS3±53±4NS11 iso(-) pts (73%) had a therapeutic response to β-blockade compared with 46 iso(+) pts (98%, p=0.01); the orthostatic ΔHR in the iso(-) pts who failed β-blocker therapy was no different from the response in the patients with a therapeutic response.ConclusionsThe HR response to orthostasis is comparably blunted after β-blockade in pts with iso(-) and iso(+) VDS, indicating that failure to respond is not due to inadequate β-blockade and suggests that in some pts iso-independent VDS may be independent of a cardiac β1 receptor mediated mechanism
Tomato yield heterosis is triggered by a dosage sensitivity of the florigen pathway that fine-tunes shoot architecture
The superiority of hybrids has long been exploited in agriculture, and although many models explaining "heterosis" have been put forth, direct empirical support is limited. Particularly elusive have been cases of heterozygosity for single gene mutations causing heterosis under a genetic model known as overdominance. In tomato (Solanum lycopersicum), plants carrying mutations in SINGLE FLOWER TRUSS (SFT) encoding the flowering hormone florigen are severely delayed in flowering, become extremely large, and produce few flowers and fruits, but when heterozygous, yields are dramatically increased. Curiously, this overdominance is evident only in the background of "determinate" plants, in which the continuous production of side shoots and inflorescences gradually halts due to a defect in the flowering repressor SELF PRUNING (SP). How sp facilitates sft overdominance is unclear, but is thought to relate to the opposing functions these genes have on flowering time and shoot architecture. We show that sft mutant heterozygosity (sft/+) causes weak semi-dominant delays in flowering of both primary and side shoots. Using transcriptome sequencing of shoot meristems, we demonstrate that this delay begins before seedling meristems become reproductive, followed by delays in subsequent side shoot meristems that, in turn, postpone the arrest of shoot and inflorescence production. Reducing SFT levels in sp plants by artificial microRNAs recapitulates the dose-dependent modification of shoot and inflorescence production of sft/+ heterozygotes, confirming that fine-tuning levels of functional SFT transcripts provides a foundation for higher yields. Finally, we show that although flowering delays by florigen mutant heterozygosity are conserved in Arabidopsis, increased yield is not, likely because cyclical flowering is absent. We suggest sft heterozygosity triggers a yield improvement by optimizing plant architecture via its dosage response in the florigen pathway. Exploiting dosage sensitivity of florigen and its family members therefore provides a path to enhance productivity in other crops, but species-specific tuning will be required
Differential Regulation of Strand-Specific Transcripts from Arabidopsis Centromeric Satellite Repeats
Centromeres interact with the spindle apparatus to enable chromosome disjunction and typically contain thousands of tandemly arranged satellite repeats interspersed with retrotransposons. While their role has been obscure, centromeric repeats are epigenetically modified and centromere specification has a strong epigenetic component. In the yeast Schizosaccharomyces pombe, long heterochromatic repeats are transcribed and contribute to centromere function via RNA interference (RNAi). In the higher plant Arabidopsis thaliana, as in mammalian cells, centromeric satellite repeats are short (180 base pairs), are found in thousands of tandem copies, and are methylated. We have found transcripts from both strands of canonical, bulk Arabidopsis repeats. At least one subfamily of 180–base pair repeats is transcribed from only one strand and regulated by RNAi and histone modification. A second subfamily of repeats is also silenced, but silencing is lost on both strands in mutants in the CpG DNA methyltransferase MET1, the histone deacetylase HDA6/SIL1, or the chromatin remodeling ATPase DDM1. This regulation is due to transcription from Athila2 retrotransposons, which integrate in both orientations relative to the repeats, and differs between strains of Arabidopsis. Silencing lost in met1 or hda6 is reestablished in backcrosses to wild-type, but silencing lost in RNAi mutants and ddm1 is not. Twenty-four–nucleotide small interfering RNAs from centromeric repeats are retained in met1 and hda6, but not in ddm1, and may have a role in this epigenetic inheritance. Histone H3 lysine-9 dimethylation is associated with both classes of repeats. We propose roles for transcribed repeats in the epigenetic inheritance and evolution of centromeres
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Improvements in the South African HIV care cascade: findings on 90-90-90 targets from successive population-representative surveys in North West Province.
IntroductionTo achieve epidemic control of HIV by 2030, countries aim to meet 90-90-90 targets to increase knowledge of HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression by 2020. We assessed the progress towards these targets from 2014 to 2016 in South Africa as expanded treatment policies were introduced using population-representative surveys.MethodsData were collected in January to March 2014 and August to November 2016 in Dr. Ruth Segomotsi Mompati District, North West Province. Each multi-stage cluster sample included 46 enumeration areas (EA), a target of 36 dwelling units (DU) per EA, and a single resident aged 18 to 49 per DU. Data collection included behavioural surveys, rapid HIV antibody testing and dried blood spot collection. We used weighted general linear regression to evaluate differences in the HIV care continuum over time.ResultsOverall, 1044 and 971 participants enrolled in 2014 and 2016 respectively with approximately 77% undergoing HIV testing. Despite increases in reported testing, known status among people living with HIV (PLHIV) remained similar at 68.7% (95% Confidence Interval (CI) = 60.9-75.6) in 2014 and 72.8% (95% CI = 63.6-80.4) in 2016. Men were consistently less likely than women to know their status. Among those with known status, PLHIV on ART increased significantly from 80.9% (95% CI = 71.9-87.4) to 91.5% (95% CI = 84.4-95.5). Viral suppression (<5000 copies/mL using DBS) among those on ART increased significantly from 55.0% (95% CI = 39.6-70.4) in 2014 to 81.4% (95% CI = 72.0-90.8) in 2016. Among all PLHIV an estimated 72.0% (95% CI = 63.8-80.1) of women and 45.8% (95% CI = 27.0-64.7) of men achieved viral suppression by 2016.ConclusionsOver a period during which fixed-dose combination was introduced, ART eligibility expanded, and efforts to streamline treatment were implemented, major improvements in the second and third 90-90-90 targets were achieved. Achieving the first 90 target will require targeted and improved testing models for men
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