Excited-state decay of hydrocarbon radicals, investigated by femtosecond time-resolved photoionization: Ethyl, propargyl, and benzyl

The excited state decay of the hydrocarbon radicals ethyl, C 2H 5; propargyl, C 3H 3; and benzyl, C 7H 7 was investigated by femtosecond time-resolved photoionization. Radicals were generated by flash pyrolysis of n-propyl nitrite, propargyl bromide, and toluene, respectively. It is shown that the 2 2A ??? (3s) Rydberg state of ethyl excited at 250 nm decays with a time constant of 20 fs. No residual signal was observed at longer delay times. For the 3 2B 1 state of propargyl excited at 255 nm a slower decay with a time constant 50??10 fs was determined. The 4 2B 2 state of benzyl excited at 255 nm decays within 150??30 fs.open242

Influence of the Location of the Internal Temperature Control Loop on the Performance of the Dual Temperature Control for Feed Temperature Disturbance

A control strategy with distributed corrective action for distillation has been proposed and consists of a conventional dual temperature control combined with an additional column tray. In this work, we evaluated the influence of the location of this internal loop as part of the new proposal, compared to a conventional system. Tests were carried out in a 13-column tray distillation equipment and feed temperature was disturbed. Two different column trays from the stripping section were used (11 and 12) for internal decentralized temperature control, each one separately, plus the dual control of top and bottom temperatures. The results demonstrated that this proposed control approach with distributed corrective action is faster than the conventional one, regardless of the column tray in use. It was also determined that the internal loop close to the feed (disturbance) is more interesting as a way to minimize transients

Reconstitution reveals how myosin-VI self-organises to generate a dynamic mechanism of membrane sculpting

One enigma in biology is the generation, sensing and maintenance of membrane curvature. Curvature-mediating proteins have been shown to induce specific membrane shapes by direct insertion and nanoscopic scaffolding, while the cytoskeletal motors exert forces indirectly through microtubule and actin networks. It remains unclear, whether the manifold direct motorprotein-lipid interactions themselves constitute another fundamental route to remodel the membrane shape. Here we show, combining super-resolution-fluorescence microscopy and membrane-reshaping nanoparticles, that curvature-dependent lipid interactions of myosin-VI on its own, remarkably remodel the membrane geometry into dynamic spatial patterns on the nano-to micrometer scale. We propose a quantitative theoretical model that explains this dynamic membrane sculpting mechanism. The emerging route of motorprotein-lipid interactions reshaping membrane morphology by a mechanism of feedback and instability opens up hitherto unexplored avenues of membrane remodelling and links cytoskeletal motors to early events in the sequence of membrane sculpting in eukaryotic cell biology

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

Reconstitution reveals how myosin-VI self-organises to generate a dynamic mechanism of membrane sculpting

One enigma in biology is the generation, sensing and maintenance of membrane curvature. Curvature-mediating proteins have been shown to induce specific membrane shapes by direct insertion and nanoscopic scaffolding, while the cytoskeletal motors exert forces indirectly through microtubule and actin networks. It remains unclear, whether the manifold direct motorprotein–lipid interactions themselves constitute another fundamental route to remodel the membrane shape. Here we show, combining super-resolution-fluorescence microscopy and membrane-reshaping nanoparticles, that curvature-dependent lipid interactions of myosin-VI on its own, remarkably remodel the membrane geometry into dynamic spatial patterns on the nano- to micrometer scale. We propose a quantitative theoretical model that explains this dynamic membrane sculpting mechanism. The emerging route of motorprotein–lipid interactions reshaping membrane morphology by a mechanism of feedback and instability opens up hitherto unexplored avenues of membrane remodelling and links cytoskeletal motors to early events in the sequence of membrane sculpting in eukaryotic cell biology. Curvature-mediating proteins are known to induce specific membrane shapes, but whether motorprotein-lipid interactions remodel membranes too remains unclear. Here authors show that curvature-dependent lipid interactions of myosin-VI remodel the membrane geometry into dynamic spatial patterns.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Mycophenolic acid in the treatment of birdshot chorioretinopathy: long-term follow-up

Aim: To assess the long-term efficacy and tolerability of both derivatives of mycophenolic acid, mycophenolate mofetil (MMF) and mycophenolate sodium (MPS), in the therapy of patients with birdshot chorioretinopathy (BSCR). Methods: Retrospective analysis of 24 patients (48 eyes) with BSCR, treated with MMF or MPS with a follow-up of at least 1 year. The main outcome measures included control of inflammation, steroid-sparing potential and side effects. Secondary outcome measure was the development of retinal function during the therapy measured by best-corrected visual acuity (BCVA), visual field and/or electroretinography (ERG). Results: Twelve patients (50%) were treated with MMF and 12 patients (50%) with MPS. Control of intraocular inflammation, defined as complete lack of clinical and angiographic signs of inflammatory activity, was achieved in 16 of 24 patients (67%). The angiographic signs of activity were significantly reduced during the follow-up (p0.05). In 20 out of 21 patients (95%) who received systemic corticosteroids, the corticosteroids could be tapered to a daily dose of ≤10 mg (rate 0.26/patient-year). Drug-related side effects occurred in 12 patients (50%, rate 0.16/patient-year). In four patients (17%), a therapy switch from MMF to MPS was undertaken due to gastrointestinal discomfort. Conclusions: Derivatives of mycophenolic acid are effective and safe drugs for the treatment of BSCR. In cases with gastrointestinal side effects, a therapy switch from MMF to MPS should be considered

Implementation of 3 T Lactate-Edited 3D 1H MR Spectroscopic Imaging with Flyback Echo-Planar Readout for Gliomas Patients

The purpose of this study was to implement a new lactate-edited 3D 1H magnetic resonance spectroscopic imaging (MRSI) sequence at 3 T and demonstrate the feasibility of using this sequence for measuring lactate in patients with gliomas. A 3D PRESS MRSI sequence incorporating shortened, high bandwidth 180° pulses, new dual BASING lactate-editing pulses, high bandwidth very selective suppression (VSS) pulses and a flyback echo-planar readout was implemented at 3 T. Over-prescription factor of PRESS voxels was optimized using phantom to minimize chemical shift artifacts. The lactate-edited flyback sequence was compared with lactate-edited MRSI using conventional elliptical k-space sampling in a phantom and volunteers, and then applied to patients with gliomas. The results demonstrated the feasibility of detecting lactate within a short scan time of 9.5 min in both phantoms and patients. Over-prescription of voxels gave less chemical shift artifacts allowing detection of lactate on the majority of the selected volume. The normalized SNR of brain metabolites using the flyback encoding were comparable to the SNR of brain metabolites using conventional phase encoding MRSI. The specialized lactate-edited 3D MRSI sequence was able to detect lactate in brain tumor patients at 3 T. The implementation of this technique means that brain lactate can be evaluated in a routine clinical setting to study its potential as a marker for prognosis and response to therapy

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment