826 research outputs found

    Epidermal growth factor receptor expression in pancreatic lesions induced in the rat by azaserine.

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    In the present study, the expression of the epidermal growth factor receptor (EGFR) was investigated in putative preneoplastic and neoplastic acinar cell lesions induced in the rat pancreas by azaserine, using Northern blotting, in situ hybridisation (ISH) and immunohistochemistry. EGFR protein levels were decreased in putative preneoplastic eosinophilic acinar cell lesions (atypical acinar cell nodules, AACN) in comparison with normal acinar cells of the pancreas. However, EGFR mRNA expression correlated positively with the volume of AACN in pancreatic homogenates and ISH showed equal or stronger EGFR mRNA expression in AACN than in the surrounding normal acinar cells. Neither EGFR protein nor EGFR mRNA was detected in more advanced lesions such as acinar adenocarcinomas (in situ). Moreover, EGFR protein expression showed an inverse relationship with the mitotic rate of the acinar cells. These findings suggest that down-regulation of EGFR at the protein level may abrogate negative constraints on cell growth, which may stimulate the development of putative preneoplastic AACN to more advanced lesions and, ultimately, acinar adenocarcinomas

    V<sub>H</sub> replacement in rearranged immunoglobulin genes

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    Examples suggesting that all or part of the V&lt;sub&gt;H&lt;/sub&gt; segment of a rearranged V&lt;sub&gt;H&lt;/sub&gt;DJ&lt;sub&gt;H&lt;/sub&gt; may be replaced by all or part of another V&lt;sub&gt;H&lt;/sub&gt; have been appearing since the 1980s. Evidence has been presented of two rather different types of replacement. One of these has gained acceptance and has now been clearly demonstrated to occur. The other, proposed more recently, has not yet gained general acceptance because the same effect can be produced by polymerase chain reaction artefact. We review both types of replacement including a critical examination of evidence for the latter. The first type involves RAG proteins and recombination signal sequences (RSS) and occurs in immature B cells. The second was also thought to be brought about by RAG proteins and RSS. However, it has been reported in hypermutating cells which are not thought to express RAG proteins but in which activation-induced cytidine deaminase (AID) has recently been shown to initiate homologous recombination. Re-examination of the published sequences reveals AID target sites in V&lt;sub&gt;H&lt;/sub&gt;-V&lt;sub&gt;H&lt;/sub&gt; junction regions and examples that resemble gene conversion

    Imaging stress and magnetism at high pressures using a nanoscale quantum sensor

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    Pressure alters the physical, chemical and electronic properties of matter. The development of the diamond anvil cell (DAC) enables tabletop experiments to investigate a diverse landscape of high-pressure phenomena ranging from the properties of planetary interiors to transitions between quantum mechanical phases. In this work, we introduce and utilize a novel nanoscale sensing platform, which integrates nitrogen-vacancy (NV) color centers directly into the culet (tip) of diamond anvils. We demonstrate the versatility of this platform by performing diffraction-limited imaging (~600 nm) of both stress fields and magnetism, up to pressures ~30 GPa and for temperatures ranging from 25-340 K. For the former, we quantify all six (normal and shear) stress components with accuracy <0.01<0.01 GPa, offering unique new capabilities for characterizing the strength and effective viscosity of solids and fluids under pressure. For the latter, we demonstrate vector magnetic field imaging with dipole accuracy <1011<10^{-11} emu, enabling us to measure the pressure-driven αϵ\alpha\leftrightarrow\epsilon phase transition in iron as well as the complex pressure-temperature phase diagram of gadolinium. In addition to DC vector magnetometry, we highlight a complementary NV-sensing modality using T1 noise spectroscopy; crucially, this demonstrates our ability to characterize phase transitions even in the absence of static magnetic signatures. By integrating an atomic-scale sensor directly into DACs, our platform enables the in situ imaging of elastic, electric and magnetic phenomena at high pressures.Comment: 18 + 50 pages, 4 + 19 figure

    Systolic blood pressure reduction during the first 24 h in acute heart failure admission: friend or foe?

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    Aims: Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results: We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last time-point available (72 h), using linear regression, and with 30- and 180-day outcomes, using Cox regression, in 1257 patients in the VERITAS study. After multivariable adjustment for baseline SBP, greater SBP decrease at 24 h from randomization was associated with greater creatinine increase at 72 h and greater risk for 30-day all-cause death, worsening heart failure (HF) or HF readmission. The hazard ratio (HR) for each 1 mmHg decrease in SBP at 24 h for 30-day death, worsening HF or HF rehospitalization was 1.01 [95% confidence interval (CI) 1.00–1.02; P = 0.021]. Similarly, the HR for each 1 mmHg decrease in SBP at 24 h for 180-day all-cause mortality was 1.01 (95% CI 1.00–1.03; P = 0.038). The associations between SBP decrease and outcomes did not differ by tezosentan treatment group, although tezosentan treatment was associated with a greater SBP decrease at 24 h. Conclusions: In the current post hoc analysis, SBP decrease during the first 24 h was associated with increased renal impairment and adverse outcomes at 30 and 180 days. Caution, with special attention to blood pressure monitoring, should be exercised when vasodilating agents are given to AHF patients

    Predictors and associations with outcomes of length of hospital stay in patients with acute heart failure: results from VERITAS

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    Background: The length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) because it prolongs an unpleasant experience for the patients and adds substantially to health care costs. Methods and Results: We examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90-day post-discharge mortality in 1347 patients with AHF enrolled in the VERITAS program. Longer LOS was associated with greater HF severity and disease burden at baseline; however, most of the variability of LOS could not be explained by these factors. LOS was associated with a higher HF risk of both HF readmission (odds ratio for 1-day increase: 1.08; 95% confidence interval [CI] 1.01–1.16; P = .019) and 90-day mortality (hazard ratio for 1-day increase: 1.05; 95% CI 1.02–1.07; P &lt; .001), although these associations are partially explained by concurrent end-organ damage and worsening heart failure during the first days of admission. Conclusions: In patients who have been admitted for AHF, longer length of hospital stay is associated with a higher rate of short-term mortality. Clinical Trial Registration: VERITAS-1 and -2: Clinicaltrials.gov identifiers NCT00525707 and NCT00524433

    Recent RHIC in-situ coating technology developments

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    To rectify the problems of electron clouds observed in RHIC and unacceptable ohmic heating for superconducting magnets that can limit future machine upgrades, we started developing a robotic plasma deposition technique for insituin-situ coating of the RHIC 316LN stainless steel cold bore tubes based on staged magnetrons mounted on a mobile mole for deposition of Cu followed by amorphous carbon (a-C) coating. The Cu coating reduces wall resistivity, while a-C has low SEY that suppresses electron cloud formation. Recent RF resistivity computations indicate that 10 {\mu}m of Cu coating thickness is needed. But, Cu coatings thicker than 2 {\mu}m can have grain structures that might have lower SEY like gold black. A 15-cm Cu cathode magnetron was designed and fabricated, after which, 30 cm long samples of RHIC cold bore tubes were coated with various OFHC copper thicknesses; room temperature RF resistivity measured. Rectangular stainless steel and SS discs were Cu coated. SEY of rectangular samples were measured at room; and, SEY of a disc sample was measured at cryogenic temperatures.Comment: 8 pages, contribution to the Joint INFN-CERN-EuCARD-AccNet Workshop on Electron-Cloud Effects: ECLOUD'12; 5-9 Jun 2012, La Biodola, Isola d'Elba, Ital

    Gene conversion in human rearranged immunoglobulin genes

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    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V&lt;sub&gt;H&lt;/sub&gt; segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V&lt;sub&gt;H&lt;/sub&gt; replacements with no addition of untemplated nucleotides at the V&lt;sub&gt;H&lt;/sub&gt;–V&lt;sub&gt;H&lt;/sub&gt; joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V&lt;sub&gt;H&lt;/sub&gt; replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

    Measurement of the diffractive structure function in deep inelastic scattering at HERA

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    This paper presents an analysis of the inclusive properties of diffractive deep inelastic scattering events produced in epep interactions at HERA. The events are characterised by a rapidity gap between the outgoing proton system and the remaining hadronic system. Inclusive distributions are presented and compared with Monte Carlo models for diffractive processes. The data are consistent with models where the pomeron structure function has a hard and a soft contribution. The diffractive structure function is measured as a function of \xpom, the momentum fraction lost by the proton, of β\beta, the momentum fraction of the struck quark with respect to \xpom, and of Q2Q^2. The \xpom dependence is consistent with the form \xpoma where a = 1.30 ± 0.08 (stat)  0.14+ 0.08 (sys)a~=~1.30~\pm~0.08~(stat)~^{+~0.08}_{-~0.14}~(sys) in all bins of β\beta and Q2Q^2. In the measured Q2Q^2 range, the diffractive structure function approximately scales with Q2Q^2 at fixed β\beta. In an Ingelman-Schlein type model, where commonly used pomeron flux factor normalisations are assumed, it is found that the quarks within the pomeron do not saturate the momentum sum rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil
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