2,116 research outputs found
Supersymmetric Dissipative Quantum Mechanics from Superstrings
Following the approach of Callan and Thorlacius applied to the superstring,
we derive a supersymmetric extension of the non-local dissipative action of
Caldeira and Leggett. The dissipative term turns out to be invariant under a
group of superconformal transformations. When added to the usual kinetic term,
it provides an example of supersymmetric dissipative quantum mechanics. As a
by-product of our analysis, an intriguing connection to the homeotic/hybrid
fermion model, proposed for CPT violation in neutrinos, appears.Comment: Latex, 16 page
NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy
Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity.
Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low.
Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes
K_S\rightarrow \gamma\gamma , K_L\rightarrow\pi^0\gamma\gamma$ and Unitarity
Agreement between the experimental value and the number predicted via a one-loop chiral perturbation
theory calculation has been cited as a success for the latter. On the other
hand the one-loop prediction for the closely related process has been found to be a factor three below the experimental
value. Using the inputs of unitarity and dispersion relations, we demonstrate
the importance of higher order loop effects to both of these processes.Comment: 20 pages (4 figures available on request), UMHEP-39
The standard model at low energies
The hadronic sector of the standard model at low energies is described by a
non--decoupling effective field theory, chiral perturbation theory. An
introduction is given to the construction of effective chiral Lagrangians, both
in the purely mesonic sector and with inclusion of baryons. The connection
between the relativistic formulation and the heavy baryon approach to chiral
perturbation theory with baryons is reviewed.Comment: Lectures given at the 6th Indian-Summer School on Intermediate Energy
Physics, Prague, Aug. 1993, Latex, 26 pages (with a4.sty), UWThPh-1993-3
Classification of Unelaborated Culinary Products: Scientific and Culinary Approaches Meet Face to Face
The ongoing academization of gastronomic studies indicates the necessity for a commonly accepted classification system for cooks that does not contradict scientific approaches. This work discusses the fundamentals used by chefs and scientists to classify unelaborated food products; proposes taxonomic gastronomy as a new interdisciplinary framework that studies the taxonomy surrounding gastronomy; and presents a categorization of unelaborated food products that follows commonly accepted culinary criteria yet avoids contradiction by scientific knowledge. As little literature focuses on these issues, and similar experiences are scarce, it is concluded that further cross-disciplinary endeavors such as this will continue to be greatly fruitful
Diagnostic accuracy and interobserver variability of CO-RADS in patients with suspected coronavirus disease-2019: a multireader validation study
Objective: To conduct a multireader validation study to evaluate the interobserver variability and the diagnostic accuracy for the lung involvement by COVID-19 of COVID-19 Reporting and Data System (CO-RADS) score. Methods: This retrospective study included consecutive symptomatic patients who underwent chest CT and reverse transcriptase-polymerase chain reaction (RT-PCR) from March 2020 to May 2020 for suspected COVID-19. Twelve readers with different levels of expertise independently scored each CT using the CO-RADS scheme for detecting pulmonary involvement by COVID-19. Receiver operating characteristic (ROC) curves were computed to investigate diagnostic yield. Fleiss’ kappa statistics was used to evaluate interreader agreement. Results: A total of 572 patients (mean age, 63 ± 20 [standard deviation]; 329 men; 142 patients with COVID-19 and 430 patients without COVID-19) were evaluated. There was a moderate agreement for CO-RADS rating among all readers (Fleiss’ K = 0.43 [95% CI 0.42–0.44]) with a substantial agreement for CO-RADS 1 category (Fleiss’ K = 0.61 [95% CI 0.60–0.62]) and moderate agreement for CO-RADS 5 category (Fleiss’ K = 0.60 [95% CI 0.58–0.61]). ROC analysis showed the CO-RADS score ≥ 4 as the optimal threshold, with a cumulative area under the curve of 0.72 (95% CI 66–78%), sensitivity 61% (95% CI 52–69%), and specificity 81% (95% CI 77–84%). Conclusion: CO-RADS showed high diagnostic accuracy and moderate interrater agreement across readers with different levels of expertise. Specificity is higher than previously thought and that could lead to reconsider the role of CT in this clinical setting. Key Points: • COVID-19 Reporting and Data System (CO-RADS) demonstrated a good diagnostic accuracy for lung involvement by COVID-19 with an average AUC of 0.72 (95% CI 67–75%). • When a threshold of ≥ 4 was used, sensitivity and specificity were 61% (95% CI 52–69%) and 81% (95% CI 76–84%), respectively. • There was an overall moderate agreement for CO-RADS rating across readers with different levels of expertise (Fleiss’ K = 0.43 [95% CI 0.42–0.44])
Pazopanib and trametinib as a synergistic strategy against osteosarcoma: Preclinical activity and molecular insights
Receptor tyrosine kinases (RTKs) inhibitors’ activity in advanced osteosarcoma is significant but short-lived. To prevent or at least delay drug resistance, we explored a vertical inhibition by combining drugs acting at different levels of the RTK pathways (pazopanib + trametinib). We studied pazopanib + trametinib antitumor activity both in vitro and in vivo (MNNG-HOS and KHOS xenografts in NOD/SCID mice) investigating the molecular mechanisms and potential escapes. The involvement of MAPK-PI3K pathways was validated by Nanostring technology, western blot and by silencing/overexpression experiments. Pazopanib targets were expressed on seven osteosarcoma cell lines and their pathways were activated. Pazopanib + trametinib exhibited synergistic antitumor activity by inducing apoptosis and inhibiting ERK1/2 and Akt. In vivo antitumor activity was shown in osteosarcoma-bearing mice. The drug combination significantly down-modulated RTK Ephrin Type-A Receptor 2 (EphA2) and Interleukin-7 Receptor (IL-7R), whereas induced mitogen-activated protein-kinase kinase (MAPKK) MEK6. EphA2 silencing significantly reduced osteosarcoma cell proliferation and migration, while impeding MEK6 up-regulation in the treated cells significantly increased the antitumor effect of the studied drugs. Moreover, the up-regulation of MEK6 reduced combination activity. Pazopanib + trametinib demonstrated synergistic antitumor effects in osteosarcoma models through ERK and Akt inhibition and EphA2 and IL-7R down-modulation. MEK6 up-regulation might evoke escaping mechanism
Electron/pion separation with an Emulsion Cloud Chamber by using a Neural Network
We have studied the performance of a new algorithm for electron/pion
separation in an Emulsion Cloud Chamber (ECC) made of lead and nuclear emulsion
films. The software for separation consists of two parts: a shower
reconstruction algorithm and a Neural Network that assigns to each
reconstructed shower the probability to be an electron or a pion. The
performance has been studied for the ECC of the OPERA experiment [1].
The separation algorithm has been optimized by using a detailed Monte
Carlo simulation of the ECC and tested on real data taken at CERN (pion beams)
and at DESY (electron beams). The algorithm allows to achieve a 90% electron
identification efficiency with a pion misidentification smaller than 1% for
energies higher than 2 GeV
Comparative physiological effects of antipsychotic drugs in children and young people: a network meta-analysis.
BACKGROUND
The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions.
METHODS
For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with Ď„, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393).
FINDINGS
Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6-8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from -2·00 kg (95% CI -3·61 to -0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI -0·70 kg/m2 (-1·21 to -0·19) with molindone to 2·03 kg/m2 (0·51 to 3·55) with quetiapine; total cholesterol -0·04 mmol/L (-0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol -0·12 mmol/L (-0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (-0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (-0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides -0·03 mmol/L (-0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from -0·09 mmol/L (-1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from -2·83 ng/mL (-8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from -0·20 bpm (-8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from -3·40 mm Hg (-6·25 to -0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from -0·61 ms (-1·47 to 0·26) with pimozide to 0·30 ms (-0·05 to 0·65) with ziprasidone.
INTERPRETATION
Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations.
FUNDING
UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation
The RING network: improvements to a GPS velocity field in the central Mediterranean
Since 2004, a continuous Global Positioning System (GPS) network has been
operated by the Istituto Nazionale di Geofisica e Vulcanologia (INGV) to
investigate active tectonic processes in Italy and the surrounding regions,
which are still largely debated. This important infrastructure is known as
Rete Integrata Nazionale GPS (RING) network, and it consists of about 130
stations that are deployed all over Italy. The development and realization of
a stable GPS monumentation, its integration with seismological instruments,
and the choice of both satellite and internet data transmission, make this
network one of the most innovative and reliable CGPS networks in the
world. The technologically advanced development of the RING network has
been accompanied by the development of different data processing strategies,
which are mainly dependent on the use of different GPS analysis software.
The different software-related solutions are here compared at different scales
for this large network, and the consistency is evaluated and quantified within
an RMS value of 0.3 mm/yr
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