Optically induced damping of the surface plasmon resonance in gold colloids

The surface plasmon damping induced by high excitation of the electron gas is studied in femtosecond pump-and-probe experiments on gold colloids embedded in a sol-gel matrix. Optical excitation of single-particle interband transitions leads to a pronounced broadening of the surface plasmon line. A similar behavior is observed for resonant excitation of the surface plasmon. This broadening is the dominant optical nonlinearity of the system, and reflects the excitation-induced damping of the surface plasmon resonance. The time evolution of the damping rate follows that of the electronic scattering rate

Communication: In search of four-atom chiral metal clusters

A combined study utilizing anion photoelectron spectroscopy and density functional theory was conducted to search for four-atom, chiral, metal, and mostly metal clusters. The clusters considered were AuCoMnBi−/0, AlAuMnO−/0, AgMnOAl−/0, and AuAlPtAg−/0, where the superscripts, −/0, refer to anionic and neutral cluster species, respectively. Based on the agreement of experimentally and theoretically determined values of both electron affinities and vertical detachment energies, the calculated cluster geometries were validated and examined for chirality. Among both anionic and neutral clusters, five structures were identified as beingchiral

Extensive sequential polymorphic interconversion in the solid-state: Two hydrates and ten anhydrous phases of hexamidine diisethionate

Crystal polymorphism and solvent inclusion is a dominant research area in the pharmaceutical industry and continues to unveil complex systems. Here, we present the solid-state system of hexamidine diisethionate (HDI), an antiseptic drug compound forming a dimorphic dihydrate as well as ten anhydrous polymorphs. The X-ray and neutron crystal structures of the hydrated crystal forms and related interaction energies show no direct interaction between the cation and water but very strong interactions between cation and anion, and anion and water. This is observed macroscopically as high stability of the hydrate against dehydration by temperature and humidity. The anhydrous polymorphs reveal a rare case of sequential and reversible polymorphic transformations, which are characterized by thermal analysis and variable-temperature powder X-ray diffraction (PXRD). While most transitions are accompanied by significant structural changes, the low-energy transitions can only be detected as slight changes in the reflection positions with temperature. HDI thus represents a model compound to investigate polymorphic transitions with small structural changes

Generation of an induced pluripotent stem cell line (MHHi018-A) from a patient with Cystic Fibrosis carrying p.Asn1303Lys (N1303K) mutation

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene which encodes for a chloride ion channel regulating the balance of salt and water across secretory epithelia. Here we generated an iPSC line from a CF patient homozygous for the p.Asn1303Lys mutation, a Class II folding defect mutation. This iPSC line provides a useful resource for disease modeling and to investigate the pharmacological response to CFTR modulators in iPSC derived epithelia

Genome-wide transcription start site mapping of Bradyrhizobium japonicum grown free-living or in symbiosis – a rich resource to identify new transcripts, proteins and to study gene regulation

Background: Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinformatics challenge. We performed dRNA-seq of Bradyrhizobium japonicum USDA 110, the nitrogen-fixing symbiont of soybean, and developed algorithms to map TSSs and promoters. Results: A specialized machine learning procedure for TSS recognition allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4329 in symbiosis with soybean and 2766 in both conditions. Further, we provide proteomic evidence for 4090 proteins, among them 107 proteins corresponding to new genes and 178 proteins with N-termini different from the existing annotation (72 and 109 of them with TSS support, respectively). Guided by proteomics evidence, previously identified TSSs and TSSs experimentally validated here, we assign a score threshold to flag 14 % of the mapped TSSs as a class of lower confidence. However, this class of lower confidence contains valid TSSs of low-abundant transcripts. Moreover, we developed a de novo algorithm to identify promoter motifs upstream of mapped TSSs, which is publicly available, and found motifs mainly used in symbiosis (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). Mapped TSSs and putative promoters, proteomic evidence and updated gene annotation were combined into an annotation file. Conclusions: The genome-wide TSS and promoter maps along with the extended genome annotation of B. japonicum represent a valuable resource for future systems biology studies and for detailed analyses of individual non-coding transcripts and ORFs. Our data will also provide new insights into bacterial gene regulation during the agriculturally important symbiosis between rhizobia and legumes

MEDB-41. Identifying a subgroup of patients with early childhood sonic hedgehog-activated medulloblastoma with unfavorable prognosis after treatment with radiation-sparing regimens including intraventricular methotrexate [Abstract]

PURPOSE/METHODS: Clinical and molecular risk factors in 142 patients 3 years] 47% vs 85% [<1 year] vs 84% [1-3 years], p<0.001). No TP53 mutations were detected (n=47). DNA methylation classification identified three subgroups: SHH-1(v12.3) (n=39), SHH-2(v12.3) (n=19), and SHH-3(v12.3) (n=19), with distinct cytogenetic profiles (chromosome 2 gains in SHH-1(v12.3), very few alterations in SHH-2(v12.3), and chromosome 9q losses in SHH-3(v12.3)), age profiles (median age [years] SHH-1(v12.3): 1.7, SHH-2(v12.3): 0.9, SHH-3(v12.3): 3.0, p<0.001), and histological distribution (SHH-2(v12.3): 74% MBEN, SHH-1(v12.3)/SHH-3(v12.3): 77%/79% DMB, p<0.001). PFS was more unfavorable in patients with SHH-3(v12.3)-medulloblastoma (5-year PFS 53% vs 86% [SHH-1(v12.3)] vs 95% [SHH-2(v12.3)], p=0.002), which remained the only risk factor on multivariable Cox regression for PFS. OS was comparable (5-year OS 94% [SHH-3(v12.3)] vs 97% [SHH-1(v12.3)] vs 100% [SHH-2(v12.3)], p=0.6). 8/9 patients with SHH-3(v12.3)-medulloblastoma received radiotherapy at relapse (6 craniospinal, 2 local [1 Gorlin syndrome, 1 BRCA2 germline mutation], 1 no radiotherapy [Gorlin syndrome]). CONCLUSION: We identify patients with an increased risk of relapse when treated with radiation-sparing approaches among children with early childhood SHH-medulloblastoma. If these tumors differ from SHH-3-medulloblastoma typically described in older children remains to be verified. Treatment recommendations need to consider cancer predisposition syndromes

Neurosurgical morbidity in pediatric supratentorial midline low‐grade glioma: results from the German LGG studies

Surgical resection is a mainstay of treatment for pediatric low-grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Records were retrospectively analyzed from 318 patients with SML-LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020. Exactly 537 operations (230 resections, 167 biopsies, 140 nontumor procedures) were performed in 318 patients (54% male, median age: 7.6 years at diagnosis, 9.5 years at operation, 11% NF1, 42.5% optic pathway glioma). Surgical mortality rate was 0.93%. Applying the Drake classification, postoperative surgical morbidity was observed following 254/537 (47.3%) and medical morbidity following 97/537 (18.1%) patients with a 40.1% 30-day persistence rate for newly developed neurological deficits (65/162). Neuroendocrine impairment affected 53/318 patients (16.7%), visual deterioration 34/318 (10.7%). Postsurgical morbidity was associated with patient age <3 years at operation, tumor volume ≥80 cm3, presence of hydrocephalus, complete resection, surgery in centers with less than median reported tumor-related procedures and during the earlier study period between 1998 and 2006, while the neurosurgical approach, tumor location, NF1 status or previous nonsurgical treatment were not. Neurosurgery-associated morbidity was frequent in pediatric patients with SML-LGG undergoing surgery in the German LGG-studies. We identified patient- and institution-associated factors that may increase the risk for complications. We advocate that local multidisciplinary teams consider the planned extent of resection and surgical skills

The impact of heavy-quark loops on LHC dark matter searches

If only tree-level processes are included in the analysis, LHC monojet searches give weak constraints on the dark matter-proton scattering cross section arising from the exchange of a new heavy scalar or pseudoscalar mediator with Yukawa-like couplings to quarks. In this letter we calculate the constraints on these interactions from the CMS 5.0/fb and ATLAS 4.7/fb searches for jets with missing energy including the effects of heavy-quark loops. We find that the inclusion of such contributions leads to a dramatic increase in the predicted cross section and therefore a significant improvement of the bounds from LHC searches.Comment: 12 pages, 1 table, 3 figures, v2: extended discussion and improved relic density calculation - matches published versio

Kinetic oxygen measurements by CVC96 in L-929 cell cultures

Generally animal and human cells use oxygen during their whole life. Consequently the oxygen use is a simple indicator to test the vitality of cells. When the vitality decreases by the delivery of toxic substances the decrease can be observed directly by the oxygen-use of the cells. To get fast information of the vitality of cells we have measured the O(2)-tension by testing a new model of a bioreactor, the Cell Vitality Checker 96 (CVC96), in practical application. With this CVC96, soon a simple test will exist for the measurement of the oxygen use. In this respect the question had to be answered whether the use in the laboratory is easy and whether oxygen as a parameter in the vitality test can also be applied in future for problems in the field of material testing

Identification of low and very high-risk patients with non-WNT/non-SHH medulloblastoma by improved clinico-molecular stratification of the HIT2000 and I-HIT-MED cohorts

Molecular groups of medulloblastoma (MB) are well established. Novel risk stratification parameters include Group 3/4 (non-WNT/non-SHH) methylation subgroups I-VIII or whole-chromosomal aberration (WCA) phenotypes. This study investigates the integration of clinical and molecular parameters to improve risk stratification of non-WNT/non-SHH MB. Non-WNT/non-SHH MB from the HIT2000 study and the HIT-MED registries were selected based on availability of DNA-methylation profiling data. MYC or MYCN amplification and WCA of chromosomes 7, 8, and 11 were inferred from methylation array-based copy number profiles. In total, 403 non-WNT/non-SHH MB were identified, 346/403 (86%) had a methylation class family Group 3/4 methylation score (classifier v11b6) ≥ 0.9, and 294/346 (73%) were included in the risk stratification modeling based on Group 3 or 4 score (v11b6) ≥ 0.8 and subgroup I-VIII score (mb_g34) ≥ 0.8. Group 3 MB (5y-PFS, survival estimation ± standard deviation: 41.4 ± 4.6%; 5y-OS: 48.8 ± 5.0%) showed poorer survival compared to Group 4 (5y-PFS: 68.2 ± 3.7%; 5y-OS: 84.8 ± 2.8%). Subgroups II (5y-PFS: 27.6 ± 8.2%) and III (5y-PFS: 37.5 ± 7.9%) showed the poorest and subgroup VI (5y-PFS: 76.6 ± 7.9%), VII (5y-PFS: 75.9 ± 7.2%), and VIII (5y-PFS: 66.6 ± 5.8%) the best survival. Multivariate analysis revealed subgroup in combination with WCA phenotype to best predict risk of progression and death. The integration of clinical (age, M and R status) and molecular (MYC/N, subgroup, WCA phenotype) variables identified a low-risk stratum with a 5y-PFS of 94 ± 5.7 and a very high-risk stratum with a 5y-PFS of 29 ± 6.1%. Validation in an international MB cohort confirmed the combined stratification scheme with 82.1 ± 6.0% 5y-PFS in the low and 47.5 ± 4.1% in very high-risk groups, and outperformed the clinical model. These newly identified clinico-molecular low-risk and very high-risk strata, accounting for 6%, and 21% of non-WNT/non-SHH MB patients, respectively, may improve future treatment stratification