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1.
Opt Express ; 27(16): 22385-22392, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510533

RESUMO

We present a phase-stabilized attosecond pump-probe beamline involving two separate infrared wavelengths for high-harmonic generation (HHG) and pump or probe. The output of a Ti:sapphire laser is partly used to generate attosecond pulses via HHG and partly to pump an optical parametric amplifier (OPA) that converts the primary Ti:sapphire radiation to a longer wavelength. The attosecond pulse and down-converted infrared are recombined after a more than 20-m-long Mach-Zehnder interferometer that spans across two laboratories and separate optical tables. We demonstrate a technique for active stabilization of the relative phase of the pump and probe to within 450 as rms, without the need for an auxiliary continuous wave (cw) laser. The long-term stability of our system is demonstrated with an attosecond photoelectron streaking experiment. While the technique has been shown for one specific OPA output wavelength (1560 nm), it should also be applicable to other OPA output wavelengths. Our setup design permits tuning of the OPA wavelength independently from the attosecond pulse generation. This approach yields new possibilities for studying the wavelength-dependence of field-driven attosecond electron dynamics in various systems.

2.
Pathologe ; 40(Suppl 3): 244-251, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31797045

RESUMO

In current routine diagnostics, the gold standard to determine the genomic profile of colorectal cancers (CRCs) is using biopsy or surgically resected tissues. However, such a tissue sample cannot represent the entire tumour heterogeneity, because it only shows a local and temporal snapshot. As a complement to tumour tissue genotyping, liquid biopsies enable minimally invasive detection of all potential tumour-specific mutations and their dynamic changes for molecular profiling. Furthermore, they can be repeated in certain intervals for monitoring response to treatment, occurrence of drug resistance and detection of relapse. This review focusses on analyzing circulating cell-free tumour DNA (ctDNA), which is mostly released from apoptotic or necrotic tumour cells into the bloodstream or by active secretion of circulating tumour cells (CTCs). Nevertheless, there are some challenges in analyzing ctDNA. First, ctDNA represents only a small fraction of total circulating DNA, because there is an enormous wild-type background of cell-free DNA (cfDNA) released by healthy cells. Second, ctDNA is highly fragmented and the amount of ctDNA in the blood is very low. In this review, we discuss the potential, fields of application as well as challenges and limitations of liquid biopsy approaches. In more detail, we discuss the possibility of using liquid biopsies as a future application for molecular characterization of CRCs, particularly for monitoring CRC patients during anti-EGFR therapy to detect resistance mutations (e.g. KRAS mutations) or further therapy-relevant mutations. In addition, we investigate whether blood-based molecular profiling is a reliable addition to routine diagnostic approaches of tissue-based molecular characterization.


Assuntos
DNA Tumoral Circulante , Neoplasias Colorretais , Células Neoplásicas Circulantes , Biomarcadores Tumorais , DNA Tumoral Circulante/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Biópsia Líquida , Mutação , Recidiva Local de Neoplasia
3.
Phys Rev Lett ; 121(8): 087206, 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30192573

RESUMO

Prior to the development of pulsed lasers, one assigned a single local temperature to the lattice, the electron gas, and the spins. With the availability of ultrafast laser sources, one can now drive the temperature of these reservoirs out of equilibrium. Thus, the solid shows new internal degrees of freedom characterized by individual temperatures of the electron gas T_{e}, the lattice T_{l} and the spins T_{s}. We demonstrate an analogous behavior in the spin polarization of a ferromagnet in an ultrafast demagnetization experiment: At the Fermi energy, the polarization is reduced faster than at deeper in the valence band. Therefore, on the femtosecond time scale, the magnetization as a macroscopic quantity does not provide the full picture of the spin dynamics: The spin polarization separates into different parts similar to how the single temperature paradigm changed with the development of ultrafast lasers.

4.
BMC Gastroenterol ; 18(1): 75, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29855275

RESUMO

BACKGROUND: Adenocarcinomas or combined adeno-neuroendocrine carcinomas (MANEC) of small bowel usually have a dismal prognosis with limited systemic therapy options. This is the first description of a patient showing a germline-related BRCA1 mutated MANEC of his ileum. The tumor presented a susceptibility to a combined chemotherapy and the PARP1-inhibitor olaparib. CASE PRESENTATION: A 74-year old male patient presented with a metastasized MANEC of his ileum. Due to clinical symptoms his ileum-tumor and the single brain metastasis were removed. We verified the same pathogenic (class 5) BRCA1 mutation in different tumor locations. There was no known personal history of a previous malignant tumor. Nevertheless we identified his BRCA1 mutation as germline-related. A systemic treatment was started including Gemcitabine followed by selective internal radiotherapy (SIRT) to treat liver metastases and in the further course Capecitabine but this treatment finally failed after 9 months and all liver metastases showed progression. The treatment failure was the reason to induce an individualized therapeutic approach using combined chemotherapy of carboplatin, paclitaxel and the Poly (ADP-ribose) polymerase- (PARP)-inhibitor olaparib analogous to the treatment protocol of Oza et al. All liver metastases demonstrated with significant tumor regression after 3 months and could be removed. In his most current follow up from December 2017 (25 months after his primary diagnosis) the patient is in a very good general condition without evidence for further metastases. CONCLUSION: We present first evidence of a therapy susceptible germline-related BRCA1 mutation in small bowel adeno-neuroendocrine carcinoma (MANEC). Our findings offer a personalized treatment option. The germline background was unexpected in a 74-year old man with no previously known tumor burden. We should be aware of the familiar background in tumors of older patients as well.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Carcinoma Neuroendócrino/tratamento farmacológico , Mutação em Linhagem Germinativa , Neoplasias do Íleo/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Idoso , Neoplasias Encefálicas/secundário , Carboplatina/uso terapêutico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/secundário , Humanos , Neoplasias do Íleo/genética , Neoplasias do Íleo/patologia , Neoplasias Hepáticas/secundário , Masculino , Paclitaxel/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
5.
Ecotoxicology ; 23(7): 1172-83, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24861137

RESUMO

This study presents a series of short-term studies (total duration 48 h) of uptake and depuration of engineered nanoparticles (ENP) in neonate Daphnia magna. Gold nanoparticles (Au NP) were used to study the influence of size, stabilizing agent and feeding on uptake and depuration kinetics and animal body burdens. 10 and 30 nm Au NP with different stabilizing agents [citrate (CIT) and mercaptoundecanoic acid (MUDA)] were tested in concentrations around 0.5 mg Au/L. Fast initial uptake was observed for all studied Au NP, with CIT stabilized Au NP showing similar rates independent of size and MUDA showing increased uptake for the smaller Au NP (MUDA 10 nm > CIT 10 nm, 30 nm > MUDA 30 nm). However, upon transfer to clean media no clear trend on depuration rates was found in terms of stabilizing agent or size. Independent of stabilizing agent, 10 nm Au NP resulted in higher residual whole-animal body burdens after 24 h depuration than 30 nm Au NP with residual body burdens about one order of magnitude higher of animals exposed to 10 nm Au NP. The presence of food (P. subcapitata) did not significantly affect the body burden after 24 h of exposure, but depuration was increased. While food addition is not necessary to ensure D. magna survival in the presented short-term test design, the influence of food on uptake and depuration kinetics is essential to consider in long term studies of ENP where food addition is necessary. This study demonstrates the feasibility of a short-term test design to assess the uptake and depuration of ENP in D. magna. The findings underlines that the assumptions behind the traditional way of quantifying bioconcentration are not fulfilled when ENPs are studied.


Assuntos
Daphnia/metabolismo , Ouro/farmacocinética , Nanopartículas/metabolismo , Poluentes Químicos da Água/farmacocinética , Animais , Testes de Toxicidade Aguda
6.
Phys Rev Lett ; 111(2): 026804, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23889430

RESUMO

We demonstrate here the realization of an integrated, electrically driven, source of surface plasmon polaritons. Light-emitting individual single-walled carbon nanotube field effect transistors were fabricated in a plasmonic-ready platform. The devices were operated at ambient conditions to act as an electroluminescence source localized near the contacting gold electrodes. We show that photon emission from the semiconducting channel can couple to propagating surface plasmons developing in the electrical terminals. Our results show that a common functional element can be operated for two different platforms emphasizing thus the high degree of compatibility between state-of-the-art nano-optoelectronics devices and a plasmonic architecture.

7.
Rev Sci Instrum ; 91(6): 063001, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611013

RESUMO

We present a compact setup for spin-, time-, and angle-resolved photoemission spectroscopy. A 10 kHz titanium sapphire laser system delivers pulses of 20 fs duration, which drive a high harmonic generation-based source for ultraviolet photons at 21 eV for photoemission. The same laser also excites the sample for pump-probe experiments. Emitted electrons pass through a hemispherical energy analyzer and a spin-filtering element. The latter is based on spin-polarized low-energy electron diffraction on an Au-passivated iridium crystal. The performance of the measurement system is discussed in terms of the resolution and efficiency of the spin filter, which are higher than those for Mott-based techniques.

8.
Urologe A ; 59(3): 318-325, 2020 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-31541269

RESUMO

BACKGROUND: Technical advancement and availability of high-throughput analysis has advanced molecular subtyping of most cancers. Thus, new possibilities for precision oncology have emerged. AIM: Therefore, we aimed to collect data regarding availability and use of next generation sequencing (NGS) for urothelial cancer within the uropathology working group of the German Society of Pathology. METHODS: We collected data by questionnaires and additionally asked for sequencing results of bladder cancers in the participating institutions. RESULTS: A total of 13 university-affiliated institutes of pathology took part in the survey. All university institutes offer NGS-based molecular panel diagnostics and provide panels covering between 15 and 170 genes. Altogether, only 20 bladder cancers were sequenced in routine diagnostics and for 10 cancers potential targeted treatment options were available. DISCUSSION: So far, despite availability of NGS diagnostics at university institutes of pathology, only few bladder cancer samples have been sequenced. Based on current data from the molecular subtyping of bladder cancers, we recommend a step-by-step protocol with basic immunohistochemistry analysis and subsequent subtype-dependent analyses, e.g., alterations of the fibroblast growth factor receptors (FGFR) or comprehensive gene panel analyses.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Medicina de Precisão , Humanos , Mutação , Patologia Molecular , Inquéritos e Questionários , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
9.
Aquat Toxicol ; 86(3): 379-87, 2008 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-18190976

RESUMO

The potential of C(60)-nanoparticles (Buckminster fullerenes) as contaminant carriers in aqueous systems was studied in a series of toxicity tests with algae (Pseudokirchneriella subcapitata) and crustaceans (Daphnia magna). Four common environmental contaminants (atrazine, methyl parathion, pentachlorophenol (PCP), and phenanthrene) were used as model compounds, representing different physico-chemical properties and toxic modes of action. The aggregates of nano-C(60) formed over 2 months of stirring in water were mixed with model compounds 5 days prior to testing. Uptake and excretion of phenanthrene in 4-days-old D. magna was studied with and without addition of C(60) in aqueous suspensions. It was found that 85% of the added phenanthrene sorbed to C(60)-aggregates >200 nm whereas about 10% sorption was found for atrazine, methyl parathion, and pentachlorophenol. In algal tests, the presence of C(60)-aggregates increased the toxicity of phenanthrene with 60% and decreased toxicity of PCP about 1.9 times. Addition of C(60)-aggregates reduced the toxicity of PCP with 25% in tests with D. magna, whereas a more than 10 times increase in toxicity was observed for phenanthrene when results were expressed as water phase concentrations. Thus, results from both toxicity tests show that phenanthrene sorbed to C(60)-aggregates is available for the organisms. For atrazine and methyl parathion no statistically significant differences in toxicities could be observed in algal and daphnid tests as a result of the presence of C(60)-aggregates. In bioaccumulation studies with phenanthrene in D. magna it was found that the uptake of phenanthrene was faster when C(60) was present in suspension and that a 1.7 times higher steady-state concentration was reached in the animals. However, a very fast clearance took place when animals were transferred to clean water resulting in no accumulation of phenanthrene. This study is the first to demonstrate the influence of C(60)-aggregates on aquatic toxicity and bioaccumulation of other environmentally relevant contaminants. The data provided underline that not only the inherent toxicity of manufactured nanoparticles, but also interactions with other compounds and characterisation of nanoparticles in aqueous suspension are of importance for risk assessment of nanomaterials.


Assuntos
Clorófitas/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Fulerenos/toxicidade , Fenantrenos/toxicidade , Poluentes Químicos da Água/farmacocinética , Poluentes Químicos da Água/toxicidade , Animais , Atrazina/metabolismo , Atrazina/farmacocinética , Atrazina/toxicidade , Disponibilidade Biológica , Clorófitas/crescimento & desenvolvimento , Fulerenos/análise , Fulerenos/metabolismo , Metil Paration/metabolismo , Metil Paration/farmacocinética , Metil Paration/toxicidade , Pentaclorofenol/metabolismo , Pentaclorofenol/farmacocinética , Pentaclorofenol/toxicidade , Fenantrenos/metabolismo , Fenantrenos/farmacocinética , Suspensões , Fatores de Tempo , Poluentes Químicos da Água/metabolismo
10.
Sci Rep ; 8(1): 3933, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29500454

RESUMO

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients. Abdominal subcutaneous AT biopsies were collected before and after intervention to determine the AT transcriptome and expression of proteins involved in lipolysis, NP signaling and mitochondrial oxidative metabolism. Both sacubitril/valsartan and amlodipine treatment did not significantly induce AT transcriptional changes in pathways related to lipolysis, NP signaling and oxidative metabolism. Furthermore, protein expression of adipose triglyceride lipase (ATGL) (Ptime*group = 0.195), hormone-sensitive lipase (HSL) (Ptime*group = 0.458), HSL-ser660 phosphorylation (Ptime*group = 0.340), NP receptor-A (NPRA) (Ptime*group = 0.829) and OXPHOS complexes (Ptime*group = 0.964) remained unchanged. In conclusion, sacubitril/valsartan treatment for 8 weeks did not alter the abdominal subcutaneous AT transcriptome and expression of proteins involved in lipolysis, NP signaling and oxidative metabolism in obese hypertensive patients.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Obesidade/metabolismo , Proteínas/metabolismo , Tetrazóis/uso terapêutico , Transcriptoma , Tecido Adiposo/metabolismo , Adulto , Aminobutiratos/farmacologia , Anlodipino/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Compostos de Bifenilo , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Gordura Subcutânea/metabolismo , Tetrazóis/farmacologia , Valsartana
11.
Nat Commun ; 9(1): 1035, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29515124

RESUMO

"The technical support from SLAC Accelerator Directorate, Technology Innovation Directorate, LCLS laser division and Test Facility Division is gratefully acknowledged. We thank S.P. Weathersby, R.K. Jobe, D. McCormick, A. Mitra, S. Carron and J. Corbett for their invaluable help and technical assistance. Research at SLAC was supported through the SIMES Institute which like the LCLS and SSRL user facilities is funded by the Office of Basic Energy Sciences of the U.S. Department of Energy under Contract No. DE-AC02-76SF00515. The UED work was performed at SLAC MeV-UED, which is supported in part by the DOE BES SUF Division Accelerator & Detector R&D program, the LCLS Facility, and SLAC under contract Nos. DE-AC02-05-CH11231 and DE-AC02-76SF00515. Use of the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515."and"Work at BNL was supported by DOE BES Materials Science and Engineering Division under Contract No: DE-AC02-98CH10886. J.C. would like to acknowledge the support from National Science Foundation Grant No. 1207252. E.E.F. would like to acknowledge support from the U.S. Department of Energy (DOE), Office of Basic Energy Sciences (BES) under Award No. DE-SC0003678."This has been corrected in both the PDF and HTML versions of the Article.

12.
Nat Commun ; 9(1): 388, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29374151

RESUMO

Magnetostriction, the strain induced by a change in magnetization, is a universal effect in magnetic materials. Owing to the difficulty in unraveling its microscopic origin, it has been largely treated phenomenologically. Here, we show how the source of magnetostriction-the underlying magnetoelastic stress-can be separated in the time domain, opening the door for an atomistic understanding. X-ray and electron diffraction are used to separate the sub-picosecond spin and lattice responses of FePt nanoparticles. Following excitation with a 50-fs laser pulse, time-resolved X-ray diffraction demonstrates that magnetic order is lost within the nanoparticles with a time constant of 146 fs. Ultrafast electron diffraction reveals that this demagnetization is followed by an anisotropic, three-dimensional lattice motion. Analysis of the size, speed, and symmetry of the lattice motion, together with ab initio calculations accounting for the stresses due to electrons and phonons, allow us to reveal the magnetoelastic stress generated by demagnetization.

13.
Nat Commun ; 8: 15461, 2017 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-28580940

RESUMO

Free-electron lasers providing ultra-short high-brightness pulses of X-ray radiation have great potential for a wide impact on science, and are a critical element for unravelling the structural dynamics of matter. To fully harness this potential, we must accurately know the X-ray properties: intensity, spectrum and temporal profile. Owing to the inherent fluctuations in free-electron lasers, this mandates a full characterization of the properties for each and every pulse. While diagnostics of these properties exist, they are often invasive and many cannot operate at a high-repetition rate. Here, we present a technique for circumventing this limitation. Employing a machine learning strategy, we can accurately predict X-ray properties for every shot using only parameters that are easily recorded at high-repetition rate, by training a model on a small set of fully diagnosed pulses. This opens the door to fully realizing the promise of next-generation high-repetition rate X-ray lasers.

14.
Cancer Res ; 35(12): 3698-704, 1975 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1192428

RESUMO

Hormone-dependent mammary tumors were induced in virgin GR mice by treatment with estrone and progesterone. Discontinuation of hormonal treatment was followed by regression of the tumor. This response to hormone treatment was also observed in the first transplant generation in inbred syngeneic hosts, but after several transplantations the tumor growth became hormone independent. The hormone dependence of the primary tumors and tumors after a single transplantation was demonstrated by growth curves. Furthermore, the cell proliferation kinetics has been investigated in a growing as well as in a regressing hormone-dependent tumor after a single transplantation from the same primary tumor. The experimental data consist of growth curves, percentage-labeled mitoses curves, and labeling indices. Since these data do not contain information concerning the localization of the cell loss in the cell cycle, they were analyzed by a computer method based on three mathematical models differing in respect to the mode of cell loss. All three models gave approximately the same estimates of the cell kinetic parameters in the growing as well as the regressing tumor. The results for the growing, hormone-dependent tumor showed a growth fraction of 62%, a cell production rate of 3.4%/hr, and a cell loss rate of 2.3%/hr. Regression of the tumor after hormonal deprivation was accompanied by a decrease in growth fraction to 18% and a decrease in the cell production rate to 0.9%/hr, while the cell loss rate was unchanged at 2.8%/hr. Furthermore, the discontinuation of hormonal treatment introduced an increase in the mean transit time of the cell cycle, particularly in the mean transit time of the G1 phase. The results might indicate that estrone and progesterone treatment stimulated growth of hormone-dependent GR mouse mammary tumors mainly by an increase of growth fraction and cell production rate.


Assuntos
Estrona/farmacologia , Neoplasias Mamárias Experimentais/patologia , Progesterona/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Feminino , Masculino , Neoplasias Mamárias Experimentais/induzido quimicamente , Camundongos , Modelos Biológicos , Transplante de Neoplasias , Transplante Homólogo
15.
Rev Sci Instrum ; 87(8): 083113, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27587106

RESUMO

A non-destructive diagnostic method for the characterization of circularly polarized, ultraintense, short wavelength free-electron laser (FEL) light is presented. The recently installed Delta undulator at the LCLS (Linac Coherent Light Source) at SLAC National Accelerator Laboratory (USA) was used as showcase for this diagnostic scheme. By applying a combined two-color, multi-photon experiment with polarization control, the degree of circular polarization of the Delta undulator has been determined. Towards this goal, an oriented electronic state in the continuum was created by non-resonant ionization of the O2 1s core shell with circularly polarized FEL pulses at hν ≃ 700 eV. An also circularly polarized, highly intense UV laser pulse with hν ≃ 3.1 eV was temporally and spatially overlapped, causing the photoelectrons to redistribute into so-called sidebands that are energetically separated by the photon energy of the UV laser. By determining the circular dichroism of these redistributed electrons using angle resolving electron spectroscopy and modeling the results with the strong-field approximation, this scheme allows to unambiguously determine the absolute degree of circular polarization of any pulsed, ultraintense XUV or X-ray laser source.

16.
Plant Biol (Stuttg) ; 7(3): 228-37, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15912442

RESUMO

Gene targeting in the moss Physcomitrella patens has created a new platform for plant functional genomics. We produced a mutant collection of 73 329 Physcomitrella plants and evaluated the phenotype of each transformant in comparison to wild type Physcomitrella. Production parameters and morphological changes in 16 categories, such as plant structure, colour, coverage with gametophores, cell shape, etc., were listed and all data were compiled in a database (mossDB). Our mutant collection consists of at least 1804 auxotrophic mutants which showed growth defects on minimal Knop medium but were rescued on supplemented medium. 8129 haploid and 11 068 polyploid transformants had morphological alterations. 9 % of the haploid transformants had deviations in the leaf shape, 7 % developed less gametophores or had a different leaf cell shape. Other morphological deviations in plant structure, colour, and uniformity of leaves on a moss colony were less frequently observed. Preculture conditions of the plant material and the cDNA library (representing genes from either protonema, gametophore or sporophyte tissue) used to transform Physcomitrella had an effect on the number of transformants per transformation. We found correlations between ploidy level and plant morphology and growth rate on Knop medium. In haploid transformants correlations between the percentage of plants with specific phenotypes and the cDNA library used for transformation were detected. The number of different cDNAs present during transformation had no effect on the number of transformants per transformation, but it had an effect on the overall percentage of plants with phenotypic deviations. We conclude that by linking incoming molecular, proteome, and metabolome data of the transformants in the future, the database mossDB will be a valuable biological resource for systems biology.


Assuntos
Bryopsida/genética , Biblioteca Gênica , Mutação , Bryopsida/fisiologia , Técnicas de Cultura de Células , DNA Complementar/genética , DNA de Plantas/genética , Bases de Dados de Ácidos Nucleicos , Mutagênese Insercional , Fenótipo , Plasmídeos/genética
17.
Nanoscale ; 7(4): 1479-84, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25504356

RESUMO

We demonstrate efficient coupling between plasmons in a single silver nanowire and nanocrystals doped with rare earth ions, α-NaYF4:Er(3+)/Yb(3+). Plasmonic interaction results in a sevenfold increase of the up-converted emission of nanocrystals located in the vicinity of the nanowires as well as much faster luminescence decays. The enhancement of the emission can be precisely controlled by the polarization of the excitation laser and is significantly stronger for polarization parallel to the nanowire antennas. Imaging of angular-resolved emission patterns in the Fourier plane reveals plasmon-mediated luminescence, where the up-converted radiation is emitted via the nanowire antennas as leakage radiation.

18.
Neurosci Lett ; 589: 159-62, 2015 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-25576705

RESUMO

Even if more extensively investigated in affective disorders, the serotonergic system is likely to be also implicated in modulating the pathogenesis of schizophrenia, where it closely interacts with the dopaminergic and glutamatergic system. To substantiate this notion, we studied the intensity and dynamics of cellular Ca(2+) responses to serotonin (5-hydoxytryptamine, 5-HT) in peripheral lymphocytes taken from currently non-psychotic schizophrenic patients. To this aim, peripheral lymphocytes were freshly obtained from healthy controls and a naturalistic collective of patients with schizophrenia in remission. Intracellular Ca(2+) responses were recorded in real-time by ratiometric fluorometry after 5-HT or phythaemagglutinin (PHA) stimulation, which served as an internal reference for Ca(2+) responsivity to non-specific stimulation. The intracellular Ca(2+) peak early after applying the 5-HT trigger was significantly elevated in schizophrenic patients. No significant differences of Ca(2+) peak levels were seen in response to stimulation with the mitogenic agent PHA, although responses to 5-HT and PHA were positively correlated in individual patients or controls. In conclusion, the serotonergic response patterns in peripheral lymphocytes from schizophrenic patients seem to be elevated, if employing sensitive tools like determination of intracellular Ca(2+) responses. Our observations suggest that the participation of serotonergic neurotransmitter system in the pathogenesis of schizophrenia may deserve more interest, even if it should only act as a modulator on the main pathology in the dopaminergic and glutamatergic systems. We hope that this pilot study will prompt further studies with larger patient collectives to revisit this question.


Assuntos
Cálcio/metabolismo , Receptores de Serotonina/metabolismo , Esquizofrenia/metabolismo , Linfócitos T/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Transdução de Sinais
19.
Rev Sci Instrum ; 86(7): 073702, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26233391

RESUMO

Ultrafast electron probes are powerful tools, complementary to x-ray free-electron lasers, used to study structural dynamics in material, chemical, and biological sciences. High brightness, relativistic electron beams with femtosecond pulse duration can resolve details of the dynamic processes on atomic time and length scales. SLAC National Accelerator Laboratory recently launched the Ultrafast Electron Diffraction (UED) and microscopy Initiative aiming at developing the next generation ultrafast electron scattering instruments. As the first stage of the Initiative, a mega-electron-volt (MeV) UED system has been constructed and commissioned to serve ultrafast science experiments and instrumentation development. The system operates at 120-Hz repetition rate with outstanding performance. In this paper, we report on the SLAC MeV UED system and its performance, including the reciprocal space resolution, temporal resolution, and machine stability.

20.
Eur J Pharmacol ; 366(1): 19-26, 1999 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-10064147

RESUMO

The influence of controllable painless stress and clomipramine treatment was evaluated on masticatory behaviour and myosin heavy chain expression in masticatory rat muscles: anterior digastric, anterior temporalis and masseter superficialis. The adult fast isoforms of myosin heavy chains detected were myosin heavy chains 2A, 2X and 2B. The myosin heavy chains composition of anterior temporalis muscle was unchanged by stress or by treatment. In anterior digastric and masseter superficialis muscles, stress induced an increase in 2B and a decrease in 2X and 2A. Under stress, whereas the myosin heavy chains composition of anterior temporalis and anterior digastric muscles was unaffected by clomipramine, this drug modified significantly the myosin heavy chains composition of masseter superficialis muscle which became comparable to that of control muscle. Stress-induced myosin heavy chains transformations led to an increased velocity of anterior digastric and masseter superficialis muscles but not anterior temporalis muscle. Gnawing and mastication were increased by stress and incisor grinding was reduced. Stress shortened the duration of gnawing and increased the fatigability of anterior digastric and masseter superficialis muscles, whereas clomipramine increased the duration of mastication and reduced the fatigability of masseter superficialis muscle. Stress produces selective changes in masticatory muscles and behaviour. This study demonstrates the muscle type-specific protective effect of clomipramine against stress-induced structural transformations of masseter superficialis muscle and the specific concomitant behavioural modifications.


Assuntos
Mastigação/fisiologia , Músculos da Mastigação/química , Estresse Fisiológico/fisiopatologia , Animais , Antidepressivos Tricíclicos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos da radiação , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/efeitos da radiação , Clomipramina/farmacologia , Eletroforese , Feminino , Luz , Mastigação/efeitos dos fármacos , Mastigação/efeitos da radiação , Músculos da Mastigação/efeitos dos fármacos , Músculos da Mastigação/efeitos da radiação , Cadeias Pesadas de Miosina/análise , Cadeias Pesadas de Miosina/efeitos dos fármacos , Cadeias Pesadas de Miosina/efeitos da radiação , Coelhos , Ratos , Ratos Wistar
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