71 research outputs found

    Light-driven molecular motors

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    Ballistic nanofriction

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    Sliding parts in nanosystems such as Nano ElectroMechanical Systems (NEMS) and nanomotors, increasingly involve large speeds, and rotations as well as translations of the moving surfaces; yet, the physics of high speed nanoscale friction is so far unexplored. Here, by simulating the motion of drifting and of kicked Au clusters on graphite - a workhorse system of experimental relevance -- we demonstrate and characterize a novel "ballistic" friction regime at high speed, separate from drift at low speed. The temperature dependence of the cluster slip distance and time, measuring friction, is opposite in these two regimes, consistent with theory. Crucial to both regimes is the interplay of rotations and translations, shown to be correlated in slow drift but anticorrelated in fast sliding. Despite these differences, we find the velocity dependence of ballistic friction to be, like drift, viscous

    Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib

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    BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials, but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction. METHODS: Patients treated with sorafenib for HCC at 5 tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of 4 centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models. RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the 4 risk groups (OS 16.9-4.6 months). A total of 920 patients (n=615 in training set, n=305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-fetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≀0.59). CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies

    Reporting of euthanasia and physician-assisted suicide in the Netherlands: descriptive study

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    Background: An important principle underlying the Dutch Euthanasia Act is physicians' responsibility to alleviate patients' suffering. The Dutch Act states that euthanasia and physician-assisted suicide are not punishable if the attending physician acts in accordance with criteria of due care. These criteria concern the patient's request, the patient's suffering (unbearable and hopeless), the information provided to the patient, the presence of reasonable alternatives, consultation of another physician and the applied method of ending life. To demonstrate their compliance, the Act requires physicians to report euthanasia to a review committee. We studied which arguments Dutch physicians use to substantiate their adherence to the criteria and which aspects attract review committees' attention. Methods: We examined 158 files of reported euthanasia and physician-assisted suicide cases that were approved by the review committees. We studied the physicians' reports and the verdicts of the review committees by using a checklist. Results: Physicians reported that the patient's request had been well-considered because the patient was clear-headed (65%) and/or had repeated the request several times (23%). Unbearable suffering was often substantiated with physical symptoms (62%), function loss (33%), dependency (28%) or deterioration (15%). In 35%, physicians reported that there had been alternatives to relieve patients' suffering which were refused by the majority. The nature of the relationship with the consultant was sometimes unclear: the consultant was reported to have been an unknown colleague (39%), a known colleague (21%), otherwise (25%), or not clearly specified in the report (24%). Review committees relatively often scrutinized the consultation (41%) and the patient's (unbearable) suffering (32%); they had few questions about possible alternatives (1%). Conclusion: Dutch physicians substantiate their adherence to the criteria in a variable way with an emphasis on physical symptoms. The information they provide is in most cases sufficient to enable adequate review. Review committees' control seems to focus on (unbearable) suffering and on procedural issues

    Changing patterns in diagnostic strategies and the treatment of blunt injury to solid abdominal organs

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    Background: In recent years there has been increasing interest shown in the nonoperative management (NOM) of blunt traumatic injury. The growing use of NOM for blunt abdominal organ injury has been made possible because of the progress made in the quality and availability of the multidetector computed tomography (MDCT) scan and the development of minimally invasive intervention options such as angioembolization. Aim: The purpose of this review is to describe the changes that have been made over the past decades in the management of blunt trauma to the liver, spleen and kidney. Results: The management of blunt abdominal injury has changed considerably. Focused assessment with sonography for trauma (FAST) examination has replaced diagnostic peritoneal lavage as diagnostic modality in the primary survey. MDCT scanning with intravenous contrast is now the gold standard diagnostic modality in hemodynamically stable patients with intra-abdominal fluid detected with FAST. One of the current discussions in the l erature is whether a whole body MDCT survey should be implemented in the primary survey. Conclusions The progress in imaging techniques has contributed to NOM being currently the treatment of choice for hemodynamically stable patients. Angioembolization can be used as an adjunct to NOM and has increased the succe

    Acceleration of a Nanomotor: Electronic Control of the Rotary Speed of a Light-Driven Molecular Rotor

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    Facing the challenge to construct nanoscale machines, it has been noted that molecular motors stand out as essential components to provide power to such systems. The diversity of fascinating biological motors, such as the kinesin or myosin linear and ATP-ase rotary motor systems, has been a source of inspiration for the development of artificial molecular mechanical devices (such as switches, shuttles, and muscles) and a variety of elegant rotor systems. The sterically overcrowded alkenes prepared in our laboratories provided the basis for a light-driven motor. Unidirectional rotation is achieved by a combination of a photochemically mediated cis-trans isomerization followed by an irreversible thermal isomerization. The motor described here is based on the second-generation light-driven unidirectional molecular motors 1. A limitation of these molecular motors proved to be their low rotary speed. A major goal of our molecular motor program is to substantially lower the Gibbs energy of activation of the thermal isomerization, the rate-determining step for the 360° rotation around the central double bond in these overcrowded alkenes. Thus far, all attempts to decrease the thermal isomerization barriers have involved structural modifications in order to diminish steric interactions around the fjord region of the molecules. This has been achieved by the introduction of smaller-sized atoms in 1 at bridging position X or using smaller rings appended to the central alkene.

    Increased Speed Of Rotation For The Smallest Light-driven Molecular Motor: Supporting information CIF-file for C28H24

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    In this paper we present the smallest artificial light-driven molecular motor consisting of only 28 carbon and 24 hydrogen atoms. The concept of controlling directionality of rotary movement at the molecular level by introduction of a stereogenic center next to the central olefinic bond of a sterically overcrowded alkene does not only hold for molecular motors with six-membered rings, but is also applicable to achieve the unidirectional movement for molecular motors having five-membered rings. Although X-ray analyses show that the five-membered rings in the cis-and trans-isomer of the new molecular motor are nearly flat, the energy differences between the (pseudo-)diaxial and (pseudo-)diequatorial conformations of the methyl substituents in both isomers are still large enough to direct the rotation of one-half of the molecule with respect to the other half in a clockwise fashion. The full rotary cycle comprises four consecutive steps: two photochemical isomerizations each followed by a thermal helix inversion. Both photochemical cis- transisomerizations proceed with a preference for the unstable diequatorial isomers over the stable diaxial isomers. The thermal barriers for helix inversion of this motor molecule have decreased dramatically compared to its six-membered ring analogue, the half-life of the fastest step being only 18 s at room temperature.
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