Raman spectra of Ag- and Cu- photodoped chalcogenide films

Raman spectra of the chalcogenide vitreous layers (As₄₀S₆₀, As₄₀S₄₀Se₂₀, As₄₀Se₆₀ ) non-doped and photodoped by Ag, Cu were measured. The spectra were analyzed in terms of a molecular model. It was ascertained, that for the spectra of photodoped As₄₀S₆₀, As₄₀S₄₀Se₂₀ layers, the shift of the main bands to the high frequency side and the appearance of the additional scattering bands in the low frequency spectral range are characteristic features. For the spectra of photodoped As₄₀S₆₀ layers, such shift and significant increase in scattering were not observed. Variations in the Raman spectra with photodoping by Ag or Cu are consistent with the supposition concerning normal covalent and coordinative bond formation between metal additives and chalcogen atoms

Minimum message length inference of secondary structure from protein coordinate data

Motivation: Secondary structure underpins the folding pattern and architecture of most proteins. Accurate assignment of the secondary structure elements is therefore an important problem. Although many approximate solutions of the secondary structure assignment problem exist, the statement of the problem has resisted a consistent and mathematically rigorous definition. A variety of comparative studies have highlighted major disagreements in the way the available methods define and assign secondary structure to coordinate data

Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer

Purpose: The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients.Experimental Design: Patients with advanced colorectal cancer were treated with 5-FU [bolus (400 mg/m(2)) followed by a 22-h infusion (600 mg/m(2))] and LV (200 mg/m(2)) and escalating doses of SAM486A, 1-3-h infusion daily for 3 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of the combination.Results: Twenty-seven patients with metastatic colorectal cancer and 1 with pseudomyxoma peritonei were treated. Twenty-six patients received SAM486A in the combination at doses ranging from 25 to 150 mg/m(2)/day. Dose-limiting toxicity consisting of fatigue grade 3 was seen at 150 mg/m(2)/day. Other adverse events included neutropenia, hand and foot syndrome, nausea, vomiting, diarrhea, and constipation. Fifteen of 26 patients evaluable for best response according to the Southwest Oncology Group criteria achieved a partial response [8 (30%) of 26] or stable disease [9 (35%) of 26]. SAM486A did not influence the pharmacolkinetics of 5-FU, and SAM486A clearance was similar to that when used as a single agent.Conclusions: The novel molecular agent SAM486A is tolerable and safe in combination with a standard 5-FU regimen in patients with advanced colorectal cancer. The dose of SAM486A recommended for additional studies with this combination is 125 mg/m(2)/day. A disease-directed evaluation of SAM486A using this regimen is warranted

Heterologous expression screens in Nicotiana benthamiana identify a candidate effector of the wheat Yellow Rust Pathogen that associates with processing bodies

Rust fungal pathogens of wheat (Triticum spp.) affect crop yields worldwide. The molecular mechanisms underlying the virulence of these pathogens remain elusive, due to the limited availability of suitable molecular genetic research tools. Notably, the inability to perform high-throughput analyses of candidate virulence proteins (also known as effectors) impairs progress. We previously established a pipeline for the fast-forward screens of rust fungal candidate effectors in the model plant Nicotiana benthamiana. This pipeline involves selecting candidate effectors in silico and performing cell biology and protein-protein interaction assays in planta to gain insight into the putative functions of candidate effectors. In this study, we used this pipeline to identify and characterize sixteen candidate effectors from the wheat yellow rust fungal pathogen Puccinia striiformis f sp tritici. Nine candidate effectors targeted a specific plant subcellular compartment or protein complex, providing valuable information on their putative functions in plant cells. One candidate effector, PST02549, accumulated in processing bodies (P-bodies), protein complexes involved in mRNA decapping, degradation, and storage. PST02549 also associates with the P-body-resident ENHANCER OF mRNA DECAPPING PROTEIN 4 (EDC4) from N. benthamiana and wheat. We propose that P-bodies are a novel plant cell compartment targeted by pathogen effectors

The Poplar Rust-Induced Secreted Protein (RISP) Inhibits the Growth of the Leaf Rust Pathogen Melampsora larici-populina and Triggers Cell Culture Alkalinisation

Plant cells secrete a wide range of proteins in extracellular spaces in response to pathogen attack. The poplar rust-induced secreted protein (RISP) is a small cationic protein of unknown function that was identified as the most induced gene in poplar leaves during immune responses to the leaf rust pathogen Melampsora larici-populina, an obligate biotrophic parasite. Here, we combined in planta and in vitro molecular biology approaches to tackle the function of RISP. Using a RISP-mCherry fusion transiently expressed in Nicotiana benthamiana leaves, we demonstrated that RISP is secreted into the apoplast. A recombinant RISP specifically binds to M. larici-populina urediniospores and inhibits their germination. It also arrests the growth of the fungus in vitro and on poplar leaves. Interestingly, RISP also triggers poplar cell culture alkalinisation and is cleaved at the C-terminus by a plant-encoded mechanism. Altogether our results indicate that RISP is an antifungal protein that has the ability to trigger cellular responses

Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer

PURPOSE: The purpose of our study was to determine the maximum-tolerated\n dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the\n polyamine synthesis inhibitor SAM486A given in combination with\n 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients. EXPERIMENTAL\n DESIGN: Patients with advanced colorectal cancer were treated with 5-FU\n [bolus (400 mg/m(2)) followed by a 22-h infusion (600 mg/m(2))] and LV\n (200 mg/m(2)) and escalating doses of SAM486A, 1-3-h infusion daily for 3\n days. Plasma sampling was performed to characterize the pharmacokinetics\n and pharmacodynamics of the combination RESULTS: Twenty-seven patients\n with metastatic colorectal cancer and 1 with pseudomyxoma peritonei were\n treated. Twenty-six patients received SAM486A in the combination at doses\n ranging from 25 to 150 mg/m(2)/day. Dose-limiting toxicity consisting of\n fatigue grade 3 was seen at 150 mg/m(2)/day. Other adverse events included\n neutropenia, hand and foot syndrome, nausea, vomiting, diarrhea, and\n constipation. Fifteen of 26 patients evaluable for best response according\n to the Southwest Oncology Group criteria achieved a partial response [8\n (30%) of 26] or stable disease [9 (35%) of 26]. SAM486A did not influence\n the pharmacokinetics of 5-FU, and SAM486A clearance was similar to that\n when used as a single agent. CONCLUSIONS: The novel molecular agent\n SAM486A is tolerable and safe in combination with a standard 5-FU regimen\n in patients with advanced colorectal cancer. The dose of SAM486A\n recommended for additional studies with this combination is 125\n mg/m(2)/day. A disease-directed evaluation of SAM486A using this regimen\n is warranted

Host-interactor screens of Phytophthora infestans RXLR proteins reveal vesicle trafficking as a major effector-targeted process

Pathogens modulate plant cell structure and function by secreting effectors into host tissues. Effectors typically function by associating with host molecules and modulating their activities. This study aimed to identify the host processes targeted by the RXLR class of host-translocated effectors of the potato blight pathogen Phytophthora infestans. To this end, we performed an in planta protein-protein interaction screen by transiently expressing P. infestans RXLR effectors in Nicotiana benthamiana leaves followed by co-immunoprecipitation and liquid chromatography tandem mass spectrometry. This screen generated an effector-host protein interactome matrix of 59 P. infestans RXLR effectors x 586 N. benthamiana proteins. Classification of the host interactors into putative functional categories revealed over 35 biological processes possibly targeted by P. infestans. We further characterized the PexRD12/31 family of RXLR-WY effectors, which associate and co-localize with components of the vesicle trafficking machinery. One member of this family, PexRD31, increased the number of FYVE positive vesicles in N. benthamiana cells. FYVE positive vesicles also accumulated in leaf cells near P. infestans hyphae, indicating that the pathogen may enhance endosomal trafficking during infection. This interactome data set will serve as a useful resource for functional studies of P. infestans effectors and of effector-targeted host processes

Quantum Engineering With Hybrid Magnonic Systems and Materials (Invited Paper)

Quantum technology has made tremendous strides over the past two decades with remarkable advances in materials engineering, circuit design, and dynamic operation. In particular, the integration of different quantum modules has benefited from hybrid quantum systems, which provide an important pathway for harnessing different natural advantages of complementary quantum systems and for engineering new functionalities. This review article focuses on the current frontiers with respect to utilizing magnons for novel quantum functionalities. Magnons are the fundamental excitations of magnetically ordered solid-state materials and provide great tunability and flexibility for interacting with various quantum modules for integration in diverse quantum systems. The concomitant-rich variety of physics and material selection enable exploration of novel quantum phenomena in materials science and engineering. In addition, the ease of generating strong coupling with other excitations makes hybrid magnonics a unique platform for quantum engineering. We start our discussion with circuit-based hybrid magnonic systems, which are coupled with microwave photons and acoustic phonons. Subsequently, we focus on the recent progress of magnon–magnon coupling within confined magnetic systems. Next, we highlight new opportunities for understanding the interactions between magnons and nitrogen-vacancy centers for quantum sensing and implementing quantum interconnects. Lastly, we focus on the spin excitations and magnon spectra of novel quantum materials investigated with advanced optical characterization