Un tarif de tonlieu inconnu, institué par le comte de Flandre Thierry d'Alsace (1128-1168) pour le port de <i>Littersuerua</i>, précurseur du port de Damme

onderzoeksrappor

SILVR: Guided Diffusion for Molecule Generation

Computationally generating novel synthetically accessible compounds with high affinity and low toxicity is a great challenge in drug design. Machine-learning models beyond conventional pharmacophoric methods have shown promise in generating novel small molecule compounds, but require significant tuning for a specific protein target. Here, we introduce a method called selective iterative latent variable refinement (SILVR) for conditioning an existing diffusion-based equivariant generative model without retraining. The model allows the generation of new molecules that fit into a binding site of a protein based on fragment hits. We use the SARS-CoV-2 Main protease fragments from Diamond X-Chem that form part of the COVID Moonshot project as a reference dataset for conditioning the molecule generation. The SILVR rate controls the extent of conditioning and we show that moderate SILVR rates make it possible to generate new molecules of similar shape to the original fragments, meaning that the new molecules fit the binding site without knowledge of the protein. We can also merge up to 3 fragments into a new molecule without affecting the quality of molecules generated by the underlying generative model. Our method is generalizable to any protein target with known fragments and any diffusion-based model for molecule generation.Comment: paper, 20 paper, 11 figure

Pengaruh Pemberian Pgpr (Plant Growth Promoting Rhizobacteria) Pada Pertumbuhan Bud Chip Tebu (Saccharum Officinarum L.)

Produksi tebu nasional yang rendah dapat ditingkatkan dengan menggunakan teknik bud chip untuk mendapatkan bibit yang berkualitas. Teknik bud chip tebu mempunyai kendala pada daya perkecambahan yang rendah. Upaya untuk mengatasi rendahnya daya kecambah ialah melalui pemberian PGPR (Plant Growth Promoting Rhizobacteria) sebagai pemacu pertumbuhan. Penelitian ini bertujuan untuk mendapatkan komposisi terbaik dari bakteri Pseudomonas fluorescens dan Bacillus subtilis pada PGPR yang dapat meningkatkan pertumbuhan bud chip tebu. Penelitian dilakukan pada bulan Januari hingga Mei 2015 di CV. Joyo Rosan, Gurah Kediri, Jawa Timur. Metode yang digunakan adalah Rancangan Acak Kelompok dengan komposisi bakteri Pseudomonas fluorescens dan Bacillus subtilis yang berbeda sebagai faktor yang ingin diketahui pengaruhnya. Hasil penelitian menunjukkan bahwa penggunaan PGPR sebagai zat pemacu tumbuh pada bud chip varietas PS 882 mampu mempercepat pertumbuhan tanaman

Toroidal grating astigmatism of high-harmonics characterized by EUV Hartmann sensor

The beam transport of single high-order harmonics in a monochromator arrangement is studied. A toroidal grating combines spectral filtering and focusing in order to produce a small individual spot for each harmonic. Here, the effect of small deviations from perfect alignment is investigated. Experimentally, a Hartmann sensor monitors the EUV wavefront while the grating is subjected to an online alignment procedure. The obtained results are confirmed by a simple theoretical description employing optical matrix methods

Advances in cardiovascular research. 15th Annual Meeting of the European Council for Cardiovascular Research (ECCR). La Colle sur Loup, France, 8-10 October 2010

The 15th Annual Meeting of the European Council of Cardiovascular Research brought together basic and clinical scientists working in the cardiovascular field in La Colle sur Loup, France. Upfront basic and clinical research addressing the mechanisms of disease, identification of biomarkers or development of new treatments was communicated in 101 presentations, 35 of them as a part of five on-topic oral sessions and three workshops. Three keynote lectures reviewed current knowledge and the latest data about mechanosensitive channels in pressure regulation, cell therapy in cardiovascular disease and mechanisms of cardiovascular risk associated with diabetic nephropathy. This article summarizes highlights of the oral sessions, workshops and keynote lectures

Insight into the dynamics of a long-runout mass movement using single-grain feldspar luminescence in the Pokhara Valley, Nepal

Mass movements play an important role in landscape evolution of high mountain areas such as the Himalayas. Yet, establishing numerical age control and reconstructing transport dynamics of past events is challenging. To fill this research gap, we bring luminescence dating to the test in an extremely challenging environment: the Pokhara Valley in Nepal. This is challenging for two reasons: (i) the optically stimulated luminescence (OSL) sensitivity of quartz, typically the mineral of choice for dating sediments younger than 100 ka, is poor, and (ii) highly rapid and turbid conditions during mass movement transport hamper sufficient OSL signal resetting prior to deposition, which eventually results in age overestimation. Here, we first assess the applicability of single-grain feldspar dating of medieval mass movement deposits catastrophically emplaced in the Pokhara Valley. Second, we exploit the poor bleaching mechanisms to get insight into the sediment dynamics of this paleo-mass movement through bleaching proxies. The Pokhara Valley is a unique setting for our case study, considering the availability of an extensive independent radiocarbon dataset as a geochronological benchmark. Single-grain infrared stimulated luminescence (IRSL) signals were measured at 50 ∘C (IRSL-50) and post-infrared infrared stimulated luminescence signals at 150 ∘C (pIRIR-150). Our results show that the IRSL-50 signal is better bleached than the pIRIR-150 signal. A bootstrapped minimum age model (bMAM) is applied to retrieve the youngest subpopulation to estimate the paleodose. However, burial ages calculated with this paleodose overestimate the radiocarbon ages by an average factor of ∼23 (IRSL-50) and ∼72 (pIRIR-150), showing that dating of the Pokhara Formation with a single-grain approach was not successful for most samples. Some samples, however, only slightly overestimate the true emplacement age and thus could be used for a rough age estimation. Large inheritances in combination with the scatter in the single-grain dose distributions show that the sediments have been transported under extremely limited light exposure prior to deposition, which is consistent with the highly turbid nature of the sediment-laden flood and debris flows depositing the Pokhara gravels. To investigate the sediment transport dynamics in more detail, we studied three bleaching proxies: the percentage of grains in saturation 2D0 criteria, the percentage of best-bleached grains (2σ range of bMAM-De) and the overdispersion (OD). None of the three bleaching proxies indicate a spatial relationship with runout distance of the mass movement deposits. We interpret this as evidence for the lack of bleaching during transport, which reflects the catastrophic nature of the event. While not providing reliable burial ages of the Pokhara mass movement deposits, single-grain feldspar dating can potentially be used as an age range finder method. Our approach shows the potential of luminescence techniques to provide insights in sediment transport dynamics of extreme and rare mass movement events in mountainous regions.</p

Adaption of the MODIS aerosol retrieval algorithm using airborne spectral surface reflectance measurements over urban areas: A case study

MODIS (MOderate-resolution Imaging Spectroradiometer) retrievals of aerosol optical depth (AOD) are biased over urban areas, primarily because the reflectance characteristics of urban surfaces are different than that assumed by the retrieval algorithm. Specifically, the operational "dark-target" retrieval is tuned towards vegetated (dark) surfaces and assumes a spectral relationship to estimate the surface reflectance in blue and red wavelengths. From airborne measurements of surface reflectance over the city of Zhongshan, China, were collected that could replace the assumptions within the MODIS retrieval algorithm. The subsequent impact was tested upon two versions of the operational algorithm, Collections 5 and 6 (C5 and C6). AOD retrieval results of the operational and modified algorithms were compared for a specific case study over Zhongshan to show minor differences between them all. However, the Zhongshan-based spectral surface relationship was applied to a much larger urban sample, specifically to the MODIS data taken over Beijing between 2010 and 2014. These results were compared directly to ground-based AERONET (AErosol RObotic NETwork) measurements of AOD. A significant reduction of the differences between the AOD retrieved by the modified algorithms and AERONET was found, whereby the mean difference decreased from 0.27±0.14 for the operational C5 and 0.19±0.12 for the operational C6 to 0.10±0.15 and -0.02±0.17 by using the modified C5 and C6 retrievals. Since the modified algorithms assume a higher contribution by the surface to the total measured reflectance from MODIS, consequently the overestimation of AOD by the operational methods is reduced. Furthermore, the sensitivity of the MODIS AOD retrieval with respect to different surface types was investigated. Radiative transfer simulations were performed to model reflectances at top of atmosphere for predefined aerosol properties. The reflectance data were used as input for the retrieval methods. It was shown that the operational MODIS AOD retrieval over land reproduces the AOD reference input of 0.85 for dark surface types (retrieved AOD = 0.87 (C5)). An overestimation of AOD = 0.99 is found for urban surfaces, whereas the modified C5 algorithm shows a good performance with a retrieved value of AOD = 0.86