3,024 research outputs found
Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment
We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp3) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzingârather than thermolyzingâthese reagents
Moment-based parameter estimation in binomial random intersection graph models
Binomial random intersection graphs can be used as parsimonious statistical
models of large and sparse networks, with one parameter for the average degree
and another for transitivity, the tendency of neighbours of a node to be
connected. This paper discusses the estimation of these parameters from a
single observed instance of the graph, using moment estimators based on
observed degrees and frequencies of 2-stars and triangles. The observed data
set is assumed to be a subgraph induced by a set of nodes sampled from
the full set of nodes. We prove the consistency of the proposed estimators
by showing that the relative estimation error is small with high probability
for . As a byproduct, our analysis confirms that the
empirical transitivity coefficient of the graph is with high probability close
to the theoretical clustering coefficient of the model.Comment: 15 pages, 6 figure
A study of quantum decoherence in a system with Kolmogorov-Arnol'd-Moser tori
We present an experimental and numerical study of the effects of decoherence
on a quantum system whose classical analogue has Kolmogorov-Arnol'd-Moser (KAM)
tori in its phase space. Atoms are prepared in a caesium magneto-optical trap
at temperatures and densities which necessitate a quantum description. This
real quantum system is coupled to the environment via spontaneous emission. The
degree of coupling is varied and the effects of this coupling on the quantum
coherence of the system are studied. When the classical diffusion through a
partially broken torus is < hbar, diffusion of quantum particles is inhibited.
We find that increasing decoherence via spontaneous emission increases the
transport of quantum particles through the boundary.Comment: 19 pages including 6 figure
A Numerical Investigation of the Effects of Classical Phase Space Structure on a Quantum System
We present a detailed numerical study of a chaotic classical system and its
quantum counterpart. The system is a special case of a kicked rotor and for
certain parameter values possesses cantori dividing chaotic regions of the
classical phase space. We investigate the diffusion of particles through a
cantorus; classical diffusion is observed but quantum diffusion is only
significant when the classical phase space area escaping through the cantorus
per kicking period greatly exceeds Planck's constant. A quantum analysis
confirms that the cantori act as barriers. We numerically estimate the
classical phase space flux through the cantorus per kick and relate this
quantity to the behaviour of the quantum system. We introduce decoherence via
environmental interactions with the quantum system and observe the subsequent
increase in the transport of quantum particles through the boundary.Comment: 15 pages, 22 figure
Association of Sperm-Associated Antigen 5 and Treatment Response in Patients With Estrogen Receptor-Positive Breast Cancer
There is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor-positive breast cancer. Objective: To investigate the associations of sperm-associated antigen 5 (SPAG5) transcript and SPAG5 protein expressions with treatment response in systemic therapy for estrogen receptor-positive breast cancer. Design, Settings, and Participants: This retrospective cohort study included patients with estrogen receptor-positive breast cancer who received 5 years of adjuvant endocrine therapy with or without neoadjuvant anthracycline-based combination chemotherapy (NACT) derived from 11 cohorts from December 1, 1986, to November 28, 2019. The associations of SPAG5 transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association of SPAG5 mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse-free survival with SPAG5 transcript or SPAG5 protein expressions were analyzed. Data were analyzed from September 9, 2015, to November 28, 2019. Main Outcomes and Measures: The primary outcomes were breast cancer-specific survival, distal relapse-free survival, pathological complete response, and clinical response. Outcomes were examined using Kaplan-Meier, multivariable logistic, and Cox regression models. Results: This study included 12 720 women aged 24 to 78 years (mean [SD] age, 58.46 [12.45] years) with estrogen receptor-positive breast cancer, including 1073 women with SPAG5 transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women with SPAG5 transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those without SPAG5 transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51]; P < .001; protein: odds ratio, 7.32 [95% CI, 3.33-16.22]; P < .001). Adding adjuvant anthracycline chemotherapy to adjuvant endocrine therapy for SPAG5 mRNA expression in estrogen receptor-positive breast cancer was associated with prolonged 5-year distal relapse-free survival in patients without lymph node involvement (hazard ratio, 0.34 [95% CI, 0.14-0.87]; P = .03) and patients with lymph node involvement (hazard ratio, 0.35 [95% CI, 0.18-0.68]; P = .002) compared with receiving 5-year endocrine therapy alone. Mean (SD) SPAG5 transcript was found to be downregulated after 2 weeks of neoadjuvant endocrine therapy compared with pretreatment levels in 68 of 92 patients (74%) (0.23 [0.18] vs 0.34 [0.24]; P < .001). Conclusions and Relevance: These findings suggest that SPAG5 transcript and SPAG5 protein expressions could be used to guide the optimal therapies for estrogen receptor-positive breast cancer. Retrospective and prospective clinical trials are warranted
Salt stress in the renal tubules is Linked to TAL specific expression of uromodulin and an upregulation of heat shock genes
Previously, our comprehensive cardiovascular characterisation study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesised at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod(-/-) mice have significantly lower blood pressure than Umod(+/+) mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption. To date there are no studies on renal transcriptome responses to salt stress. Here we aimed to delineate salt stress pathways in tubules isolated from Umod(+/+) mice (a model of sodium retention) and Umod(-/-) mice (a model of sodium depletion) +/-300mOsmol sodium chloride (n=3 per group) performing RNA-Seq. In response to salt stress, the tubules of Umod(+/+) mice displayed an up regulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, p=2.48e-12) and Hspa1b (Log2 fold change 4.05, p=2.48e-12). This response was absent in tubules of Umod(-/-) mice. Interestingly, 7 of the genes discordantly expressed in the Umod(-/-) tubules were electrolyte transporters. Our results are the first to show that salt stress in renal tubules alters the transcriptome, increasing the expression of heat shock genes. This direction of effect in Umod(+/+) tubules suggest the difference is due to the presence of Umod facilitating greater sodium entry into the tubule cell reflecting a specific response to salt stress
A statistical network analysis of the HIV/AIDS epidemics in Cuba
The Cuban contact-tracing detection system set up in 1986 allowed the
reconstruction and analysis of the sexual network underlying the epidemic
(5,389 vertices and 4,073 edges, giant component of 2,386 nodes and 3,168
edges), shedding light onto the spread of HIV and the role of contact-tracing.
Clustering based on modularity optimization provides a better visualization and
understanding of the network, in combination with the study of covariates. The
graph has a globally low but heterogeneous density, with clusters of high
intraconnectivity but low interconnectivity. Though descriptive, our results
pave the way for incorporating structure when studying stochastic SIR epidemics
spreading on social networks
Dynamics of extracellular polymeric substance (EPS) production and loss in an estuarine, diatom-dominated, microalgal biofilm over a tidal emersion-immersion period.
We studied patterns of production and loss of four different extracellular polymeric substance (EPS) fractions - colloidal carbohydrates, colloidal EPS (cEPS), hot water (HW)-extracted and hot bicarbonate (HB)-extracted fractions - and community profiles of active (RNA) bacterial communities by use of Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis of reverse transcription-polymerase chain reaction amplified 16S rRNA in mudflats in the Colne Estuary, United Kingdom, over two tidal emersion-immersion cycles. Colloidal carbohydrates and intracellular storage carbohydrate (HW) increased during tidal emersion and declined during tidal cover. The dynamics of cEPS and uronic acid content were closely coupled, as were the HB fraction and HB uronic acids. Changes in monosaccharide profiles of HW and HB fractions occurred during the diel period, with some similarity between cEPS and HB fractions. Increasing enzymatic release rates of reducing sugars and increased reducing sugar content were correlated with increased concentrations of colloidal carbohydrate and cEPS during the illuminated emersion period, and with the amount of HB-extracted uronic acids (the most refractory EPS fraction measured). Loss of reducing sugars was high, with sediment concentrations far below those predicted by the measured in situ release rates, T-RFLP analysis revealed no significant shifts in the overall taxonomic composition of the active bacterial community. However, 12 of the 59 terminal restriction fragments identified showed significant changes in relative abundance during the tidal cycle. Changes in the relative abundance of three particular terminal restriction fragments (bacterial taxa) were positively correlated to the rate of extracellular hydrolysis. Losses of chlorophyll a and colloidal and cEPS (up to 50-60) occurred mainly in the first 30 min after tidal cover. About half of this may be owing to in situ degradation, with "wash away" into the water column accounting for the remainder. Ă© 2006, by the American Society of Limnology and Oceanography, Inc
Massive black hole remnants of the first stars in galactic haloes
We investigate the possibility that present-day galactic haloes contain a
population of massive black holes (MBHs) that form by hierarchical merging of
the black hole remnants of the first stars. Some of the MBHs may be large
enough or close enough to the centre of the galactic host that they merge
within a Hubble time. We estimate to what extent this process could contribute
to the mass of the super-massive black holes (SMBHs) observed in galactic
centres today. Many MBHs will not reach the centre of the main halo, however,
but continue to orbit within satellite subhaloes. Using a semi-analytical
approach that explicitly accounts for dynamical friction, tidal disruption and
encounters with the galactic disk, we follow the dynamics of the satellites and
their MBHs and determine the abundance and distribution of MBHs in present-day
haloes of various masses. Considering two different accretion scenarios we also
compute the bolometric luminosity function for the MBHs.Comment: Accepted for publication in MNRAS, 11 pages, 11 figure
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