Summary EGFR overexpression in salivary gland carcinomas provides the rational for the investigation of anti-EGFR treatments in recurrent and/or metastatic salivary gland cancers (RMSGCs). The ...activity of cetuximab in terms of clinical benefit rate (CBR) defined as the occurrence of objective response (CR or PR) or stable disease (SD) for ⩾6 months was investigated. From April to December 2005, 30 patients 23 adenoid cystic carcinoma (ACC) and 7 non-ACC were treated with cetuximab at 400 mg/m2 /week followed by 250 mg/m2 /week until progression, major toxicity or voluntary discontinuation. EGFR expression and gene status were retrospectively analyzed by immunocytochemistry and fluorescence in situ hybridization, respectively. A median of 14 courses of cetuximab (range 5–54) were infused. Skin toxicity was the main adverse event. Cetuximab provides a CBR in 50% (95% CL, 31 to 69%) of cases. None tumor sample showed EGFR gene amplification and an increased EGFR copy number was observed in 12% of samples, all ACC. Skin rash ⩾G2, EGFR overexpression and EGFR copy number were not statistically correlated to CB. In RMSGCs further evaluations of EGFR targeting agents are advisable and should take place by appropriate tumor biological selection, differentiating ACC from non-ACC.
Hydrogen sulfide (H2S) has been extensively studied as a signal molecule in the body for the past 30 years. Researchers have conducted studies using both natural and synthetic sources of H2S, known ...as H2S donors, which have different characteristics in terms of how they release H2S. These donors can be inorganic salts or have various organic structures. In recent years, certain types of sulfur compounds found naturally in foods have been characterized as H2S donors and explored for their potential health benefits. These compounds are referred to as "sulfanutraceuticals," a term that combines "nutrition" and "pharmaceutical". It is used to describe products derived from food sources that offer additional health advantages. By introducing the terms "sulfaceuticals" and "sulfanutraceuticals," we categorize sulfur-containing substances based on their origin and their use in both preclinical and clinical research, as well as in dietary supplements.
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ESPRESSO at VLT Pepe, F.; Cristiani, S.; Rebolo, R. ...
Astronomy and astrophysics (Berlin),
01/2021, Letnik:
645
Journal Article
Recenzirano
Odprti dostop
Context.
ESPRESSO is the new high-resolution spectrograph of ESO’s Very Large Telescope (VLT). It was designed for ultra-high radial-velocity (RV) precision and extreme spectral fidelity with the aim ...of performing exoplanet research and fundamental astrophysical experiments with unprecedented precision and accuracy. It is able to observe with any of the four Unit Telescopes (UTs) of the VLT at a spectral resolving power of 140 000 or 190 000 over the 378.2 to 788.7 nm wavelength range; it can also observe with all four UTs together, turning the VLT into a 16 m diameter equivalent telescope in terms of collecting area while still providing a resolving power of 70 000.
Aims.
We provide a general description of the ESPRESSO instrument, report on its on-sky performance, and present our Guaranteed Time Observation (GTO) program along with its first results.
Methods.
ESPRESSO was installed on the Paranal Observatory in fall 2017. Commissioning (on-sky testing) was conducted between December 2017 and September 2018. The instrument saw its official start of operations on October 1, 2018, but improvements to the instrument and recommissioning runs were conducted until July 2019.
Results.
The measured overall optical throughput of ESPRESSO at 550 nm and a seeing of 0.65″ exceeds the 10% mark under nominal astroclimatic conditions. We demonstrate an RV precision of better than 25 cm s
−1
during a single night and 50 cm s
−1
over several months. These values being limited by photon noise and stellar jitter shows that the performance is compatible with an instrumental precision of 10 cm s
−1
. No difference has been measured across the UTs, neither in throughput nor RV precision.
Conclusions.
The combination of the large collecting telescope area with the efficiency and the exquisite spectral fidelity of ESPRESSO opens a new parameter space in RV measurements, the study of planetary atmospheres, fundamental constants, stellar characterization, and many other fields.
We investigated the rest-frame spectral lags of two complete samples of bright long (50) and short (6) gamma-ray bursts (GRB) detected by Swift. We analysed the Swift/Burst Alert Telescope data ...through a discrete cross-correlation function fitted with an asymmetric Gaussian function to estimate the lag and the associated uncertainty. We find that half of the long GRBs have a positive lag and half a lag consistent with zero. All short GRBs have lags consistent with zero. The distributions of the spectral lags for short and long GRBs have different average values. Limited by the small number of short GRBs, we cannot exclude at more than 2s significance level that the two distributions of lags are drawn from the same parent population. If we consider the entire sample of long GRBs, we do not find evidence for a lag-luminosity correlation, rather the lag-luminosity plane appears filled on the left-hand side, thus suggesting that the lag-luminosity correlation could be a boundary. Short GRBs are consistent with the long ones in the lag-luminosity plane.
Electron-beam calibration of aerogel tiles for the HELIX RICH detector Allison, P.; Baiocchi, M.; Beatty, J.J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
October 2023, 2023-10-00, Letnik:
1055
Journal Article
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The HELIX cosmic-ray detector is a balloon-borne instrument designed to measure the flux of light isotopes in the energy range from 0.2 GeV/n to beyond 3 GeV/n. It will rely on a ring-imaging ...Cherenkov (RICH) detector for particle identification at energies greater than 1 GeV/n and will use aerogel tiles with refractive index near 1.15 as the radiator. To achieve the performance goals of the experiment it is necessary to know the refractive index and its position dependence over the lateral extent of the tiles to a precision of O(10−4). In this paper we describe the apparatus and methods developed to calibrate the HELIX tiles in an electron beam, in order to meet this requirement.
Summary
Background
Striae gravidarum (SG), or stretch marks of pregnancy, begin as erythematous streaks and mature into hypopigmented atrophic bands.
Objectives
In order to investigate molecular ...alterations that may promote atrophy of SG, we investigated dermal type I collagen fibrils, which provide human skin with support.
Methods
We obtained skin samples of recently developed, erythematous abdominal SG from pregnant women. To examine the organization of collagen fibrils, second‐harmonic generation imaging was performed using multiphoton microscopy. Immunostaining was used to determine protein expression and localization of type I procollagen, the precursor of type I collagen fibrils. Real‐time polymerase chain reaction was used to determine gene expression levels.
Results
In control (hip) and stretched normal‐appearing perilesional abdominal skin, dermal collagen fibrils were organized as tightly packed, interwoven bundles. In SG, collagen bundles appeared markedly separated, especially in the mid‐to‐deep dermis. In the spaces separating these bundles, loosely packed wavy collagen fibrils lacking organization as bundles were present. These disorganized fibrils persisted into the postpartum period and failed to form densely packed bundles. Numerous large fibroblasts displaying type I procollagen expression were in close proximity to the disorganized fibrils, suggesting that the fibrils are newly synthesized. Supporting this possibility, immunostaining and gene expression of type I procollagen were increased throughout the dermis of SG.
Conclusions
Early SG display marked separation of collagen bundles and emergence of disorganized collagen fibrils that fail to form bundles. These alterations may reflect ineffective repair of collagen bundles disrupted by intense skin stretching. Persistent disruption of the collagenous extracellular matrix likely promotes formation and atrophy of SG.
What's already known about this topic?
Dermal collagen fibrils are organized as densely packed bundles that provide support to human skin.
Little is known about alterations involving collagen fibrils in striae gravidarum (SG), also known as stretch marks of pregnancy.
What does this study add?
In recently developed SG, collagen bundles become markedly separated, and disorganized collagen fibrils emerge and fail to form bundles.
What is the translational message?
These alterations of collagen fibril organization likely promote atrophy.
Therapies promoting organization of collagen fibrils into densely packed bundles may improve SG.
Linked Comment: Sambi and Watson. Br J Dermatol 2018; 178:590–591.
Plain language summary available online
We present the analysis of the extraordinarily bright gamma-ray burst (GRB) 130427A under the hypothesis that the GRB central engine is an accretion-powered magnetar. In this framework, initially ...proposed to explain GRBs with precursor activity, the prompt emission is produced by accretion of matter on to a newly born magnetar, and the observed power is related to the accretion rate. The emission is eventually halted if the centrifugal forces are able to pause accretion. We show that the X-ray and optical afterglow is well explained as the forward shock emission with a jet break plus a contribution from the spin-down of the magnetar. Our modelling does not require any contribution from the reverse shock, that may still influence the afterglow light curve at radio and mm frequencies, or in the optical at early times. We derive the magnetic field (B ∼ 1016 G) and the spin period (P ∼ 20 ms) of the magnetar and obtain an independent estimate of the minimum luminosity for accretion. This minimum luminosity results well below the prompt emission luminosity of GRB 130427A, providing a strong consistency check for the scenario where the entire prompt emission is the result of continuous accretion on to the magnetar. This is in agreement with the relatively long spin period of the magnetar. GRB 130427A was a well-monitored GRB showing a very standard behaviour and, thus, is a well-suited benchmark to show that an accretion-powered magnetar gives a unique view of the properties of long GRBs.
Senescent myocardium differs from adult myocardium at both functional and cellular levels. To adjudicate the efficacy of ischemic preconditioning as an alternative or adjuvant myoprotective strategy ...a reproducible, age-independent, intact laboratory model is necessary.
Adult (0.5 to 1.0 years) and senescent (5.7 to 8.0 years) sheep underwent 60 minutes of normothermic regional ischemia with 150 minutes of reperfusion. Group II (adult-ischemic preconditioning) and group IV (aged-ischemic preconditioning) underwent preconditioning with three 5-minute episodes of normothermic regional ischemia. Group I (adult-control) and group III (aged-control) were not preconditioned.
Risk size and infarct size weights were delineated by monastryl blue pigment infusion and buffered tetrazolium solution. Ischemic preconditioning was evidenced by an infarct size reduction of 54% for adult sheep and 47% for senescent sheep (
p < 0.01 versus age-matched controls;
p = not significant for adult versus senescent).
The data suggest that the cellular pathways involved with the preconditioning response are well preserved in senescent myocardium and support the utility of the ovine heart model to investigate the clinical relevance of ischemic preconditioning for the increasingly aged population presently undergoing cardiac operations.
Abstract Dysregulation of oxidative phosphorylation is associated with increased mitochondrial reactive oxygen species production and some of the most prevalent human diseases including obesity, ...cancer, diabetes, neurodegeneration, and heart disease. Chemical 'mitochondrial uncouplers' are lipophilic weak acids that transport protons into the mitochondrial matrix via a pathway that is independent of ATP synthase, thereby uncoupling nutrient oxidation from ATP production. Mitochondrial uncouplers also lessen the proton motive force across the mitochondrial inner membrane and thereby increase the rate of mitochondrial respiration while decreasing production of reactive oxygen species. Thus, mitochondrial uncouplers are valuable chemical tools that enable the measurement of maximal mitochondrial respiration and they have been used therapeutically to decrease mitochondrial reactive oxygen species production. However, the most widely used protonophore uncouplers such as carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and 2,4-dinitrophenol have off-target activity at other membranes that lead to a range of undesired effects including plasma membrane depolarization, mitochondrial inhibition, and cytotoxicity. These unwanted properties interfere with the measurement of mitochondrial function and result in a narrow therapeutic index that limits their usefulness in the clinic. To identify new mitochondrial uncouplers that lack off-target activity at the plasma membrane we screened a small molecule chemical library. Herein we report the identification and validation of a novel mitochondrial protonophore uncoupler (2-fluorophenyl){6-(2-fluorophenyl)amino(1,2,5-oxadiazolo3,4-epyrazin-5-yl)}amine, named BAM15, that does not depolarize the plasma membrane. Compared to FCCP, an uncoupler of equal potency, BAM15 treatment of cultured cells stimulates a higher maximum rate of mitochondrial respiration and is less cytotoxic. Furthermore, BAM15 is bioactive in vivo and dose-dependently protects mice from acute renal ischemic-reperfusion injury. From a technical standpoint, BAM15 represents an effective new tool that allows the study of mitochondrial function in the absence of off-target effects that can confound data interpretation. From a therapeutic perspective, BAM15-mediated protection from ischemia-reperfusion injury and its reduced toxicity will hopefully reignite interest in pharmacological uncoupling for the treatment of the myriad of diseases that are associated with altered mitochondrial function.
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